Kit or device for detecting early stage pancreatic cancer or pancreatic cancer precursor lesions and detection method therefor

ABSTRACT

This application provides a kit or a device for the detection of early pancreatic cancer or a pancreatic cancer precursor lesion, comprising a nucleic acid(s) capable of specifically binding to a miRNA(s) in a sample from a subject, and a method for detecting early pancreatic cancer or a pancreatic cancer precursor lesion, comprising measuring an expression level(s) of the miRNA(s) in vitro.

TECHNICAL FIELD

The present invention relates to a kit or a device for the detection ofearly pancreatic cancer or a pancreatic cancer precursor lesion,comprising a nucleic acid capable of specifically binding to aparticular miRNA, which is used for examining the presence or absence ofearly pancreatic cancer or pancreatic cancer precursor lesion in asubject, and a method for detecting early pancreatic cancer or apancreatic cancer precursor lesion, comprising measuring an expressionlevel of the miRNA using the nucleic acid.

BACKGROUND ART

The pancreas serves as an exocrine gland that secretes pancreatic juiceas a digestive juice and sends the juice into the digestive tractthrough the pancreatic duct, while also functioning as an endocrinegland that secretes hormones such as insulin and glucagon into blood.

Since the pancreas is surrounded by many organs such as the stomach, theduodenum, the small intestine, the liver, and the gallbladder,pancreatic cancer is not only difficult to detect early but hasproperties such as a lack of subjective symptoms, very rapidprogression, and metastasis to other organs and thus has very poorprognosis as compared with other cancers. According to the 2011statistics of cancer type-specific mortality in Japan disclosed by theCenter for Cancer Control and Information Services, National CancerCenter (Tokyo, Japan), the number of pancreatic cancer deaths climbed to28,829 people, and 5-year relative survival rates by cancer type from2003 to 2005 were lowest in pancreatic cancer with 7.1% for males and6.9% for females.

As described in Non-Patent Literature 1, the basic therapy of pancreaticcancer is practiced by surgery, systemic chemotherapy, radiotherapy, ora combination thereof depending on a stage of progression. Although 15to 20% pancreatic cancer patients undergo surgery for potential completecure, the great majority of patients who do not undergo surgery areconsidered to have local progression or metastasis.

The UICC (Unio Internationalis Contra Cancrum) stages of progression ofpancreatic cancer are classified into stages 0, IA, IB, IIA, IIB, III,IVa, and IVb. Stages I to III occupy half or more of the number of5-year survivals, and stages IVa and IVb occupy 70% or more of thestages of progression at the time of diagnosis. As described inNon-Patent Literature 1, the 5-year survival rate of pancreatic canceris 45.8% for stage IA, 36.3% for stage IB, 29.4% for stage IIA, 10.6%for stage IIB, 5.9% for stage III, and 4.0% for stage IV, and theprognoses of stage III and stage IV are very poor. Therefore, earlydetection and treatment of pancreatic cancer are necessary.

As described in Non-Patent Literature 2, abdominal ultrasonography isvery useful as convenient and minimally invasive examination inoutpatient care or medical examination for the diagnosis of pancreaticcancer. However, it is often difficult to visualize pancreatic cancerhaving a small tumor size or a lesion on the pancreatic tail side. Inordinary medical checkup, the abnormality detection rate with pancreaticimages by abdominal ultrasonography is approximately 1%, and thedetection rate of pancreatic cancer is approximately 0.06% or lower. Forexample, CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72, and urinaryfucose as carbohydrate antigens, and CEA, POA, and TPS asnon-carbohydrate antigens are known as tumor markers for the detectionof pancreatic cancer. As for how to use these tumor markers, a subjectis suspected of having a cancer when their concentrations in blood arehigher or lower than predetermined reference values. For example, asdescribed in Non-Patent Literature 3, the reference value of CEA is setto 5 ng/mL, and the reference value of CA19-9 is set to 37 U/mL. Asubject is suspected of having a cancer including pancreatic cancer whentheir concentrations exhibit these values or higher. However, theevaluation of tumor markers mostly examines advanced pancreatic cancerand does not show abnormal values for early pancreatic cancer in manycases. Even combinatorial use of tumor markers and abdominalultrasonography in medical examination results in low rates of detectionof pancreatic cancer. The implementation of such medical examinationsfor the detection of pancreatic cancer is controversial from theviewpoint of cost effectiveness.

Meanwhile, cystic diseases that occur in the pancreas are known toprogress to invasive cancers through malignant transformation and can beregarded as pancreatic cancer precursor lesions. As described inNon-Patent Literature 4, the malignancy of the cystic diseases isevaluated on the basis of cyst diameters, wall thickening, diameters ofthe main pancreatic duct, mural nodules, stenosis of the main pancreaticduct, enlarged lymph nodes, and cystic lesions, etc. Patients withintraductal papillary-mucinous neoplasms, one type of cystic disease,have a prognosis as poor as 40.4% for malignant cancer and 30.8% forinvasive cancer and are therefore recommended to receive follow-up ortumor resection even if the malignancy of the tumors is low when thetumors are detected.

As shown in Patent Literatures 1 to 5 and Non-Patent Literature 4, thereare reports, albeit at a research stage, on the determination ofpancreatic cancer using the expression levels of microRNAs (miRNAs), orcombinations of the expression levels of miRNAs and the expressionlevels of additional protein markers in biological samples includingblood.

Patent Literature 1 discloses a method for detecting pancreatic cancerby combining hsa-miR-125a-3p, hsa-miR-204-3p, and hsa-miR-3648 withseveral other miRNAs in blood.

Patent Literature 2 discloses a method for detecting pancreatic cancerby combining miRNAs such as hsa-miR-1908-5p, hsa-miR-6729-5p, andhsa-miR-5195-3p in blood.

Patent Literature 3 discloses a method for detecting pancreatic cancerby combining miR-23a-3p with tens of other miRNAs in blood.

Patent Literature 4 lists hsa-miR-1268a, hsa-miR-939-5p, andhsa-miR-642b-3p as miRNAs that have a larger expression level in theblood of pancreatic cancer patients than that in the blood of healthysubjects and discloses a method for detecting pancreatic cancer and amethod for evaluating the risk of developing pancreatic cancer bycombining these miRNAs with tens of other miRNAs.

Patent Literature 5 discloses a method for detecting pancreatic canceror a pancreatic cancer precursor lesion and a method for evaluating therisk of developing pancreatic cancer by combining hsa-miR-296-5p withtens of other miRNAs in blood.

Non-Patent Literature 5 lists hsa-miR-638, hsa-miR-3196,hsa-miR-1225-3p, and the like as miRNAs that have a larger expressionlevel in the blood of pancreatic cancer patients than that in the bloodof healthy subjects and discloses a method for detecting pancreaticcancer by combining several these miRNAs.

PRIOR ART LITERATURE Patent Literature

-   Patent Literature 1: JP Patent Publication (Kokai) No. 2015-107091 A    (2015)-   Patent Literature 2: International Publication No. WO 2015/182781-   Patent Literature 3: Published U.S. Patent Application No.    2015/0011414-   Patent Literature 4: JP Patent Publication (Kohyo) No. 2015-502176 A    (2015)-   Patent Literature 5: International Publication No. WO 2015/153679

Non-Patent Literature

-   Non-Patent Literature 1: Tetsuya Mine, “Suizo (Pancreas), Journal of    the Japan Pancreas Society”, Japan Pancreas Society, 2007, Vol.    22, p. 10-13-   Non-Patent Literature 2: Japan Pancreas Society, “2009 Scientific    evidence based clinical practice guidelines for pancreatic cancer”    CQ1 diagnosis methods http://www.suizou.org/PCMG2009/cq1/cq1-3.html-   Non-Patent Literature 3: Kiyoshi Kurokawa et al. ed., LAB DATA,    2013, p. 633, 636 (Igaku-Shoin Ltd., Tokyo, Japan)-   Non-Patent Literature 4: Working Group of the Japan Pancreas    Society, International consensus guidelines 2012 for the management    of IPMN and MCN of the pancreas., p. 6, 8-   Non-Patent Literature 5: Miyamae M. et al., 2015, British Journal of    Cancer, Vol. 113, (10) p. 1467-1476

SUMMARY OF INVENTION Problem to be Solved by Invention

An object of the present invention is to find novel tumor markers forearly pancreatic cancer or a pancreatic cancer precursor lesion and toprovide a method that can effectively detect early pancreatic cancer ora pancreatic cancer precursor lesion using nucleic acids capable ofspecifically binding to the markers. As described in Non-PatentLiterature 2, for example, CA19-9, Span-1, CA50, CA242, Dupan-2, TAG-72,and urinary fucose as carbohydrate antigens and CEA, POA, and TPS asnon-carbohydrate antigens are known as tumor markers for the detectionof pancreatic cancer. The pancreatic cancer detection sensitivity ofthese tumor markers is 70 to 80% for CA19-9, 70 to 80% for Span-1, 50 to60% for Dupan-2, 30 to 60% for CEA, and 60% for CA50. In addition, theirspecificity is not much high, and their false positive rates are as highas 20 to 30%. Therefore, there may be the possibility of false detectionof other cancers and/or benign tumors and/or benign diseases of thepancreas and/or peripancreatic organs, etc. Particularly, the detectionsensitivity of early pancreatic cancer is generally low, and thepositive rate of CA19-9 is merely ½ (52%) for pancreatic cancer having atumor size of 2 cm or smaller. Therefore, these tumor markers are notuseful for the detection of early pancreatic cancer. Furthermore, thetumor markers based on carbohydrate antigens exhibit false negatives inLewis blood type negative cases, in which the subjects do not producethe antigens. Therefore, this examination is unsuitable for somesubjects. The detection rates of intraductal papillary-mucinousneoplasms which are pancreatic cancer precursor lesions by MRI and CTare 19.9% and 1.2 to 2.6%, respectively, and are not sufficient. Thus,use of tumor markers is not recommended for the detection of pancreaticcancer precursor lesions.

As described below, there are reports, albeit at a research stage, onthe determination of pancreatic cancer using the expression levels ofmicroRNAs (miRNAs) in biological samples including blood, none of which,however, have yet been brought into practical use as a method fordetecting early pancreatic cancer or a pancreatic cancer precursorlesion.

Patent Literature 1 discloses a method for detecting pancreatic cancerby combining miR-125a-3p, miR-204-3p, and miR-3648 with several othermiRNAs in blood. In this literature, however, only healthy subjects wereused as a negative control group for pancreatic cancer. Furthermore, theliterature neither describes cancers in organs other than the pancreasor benign diseases nor describes a specific method for detecting apancreatic cancer precursor lesion using blood.

Patent Literature 2 discloses a method for detecting pancreatic cancerby combining miRNAs such as hsa-miR-1908-5p, hsa-miR-6729-5p, andhsa-miR-5195-3p in blood. In this literature, however, only severalsamples from early pancreatic cancer patients were involved.Furthermore, the literature neither describes specific detectionperformance thereof such as accuracy, sensitivity, or specificity forearly pancreatic cancer nor describes a specific method for detecting apancreatic cancer precursor lesion using blood.

Patent Literature 3 discloses a method for detecting pancreatic cancerby combining hsa-miR-23a-3p with tens of other miRNAs in blood. Thisliterature, however, neither describes specific detection performancethereof such as accuracy, sensitivity, or specificity for earlypancreatic cancer nor describes cancers in regions other than theperipancreatic gastrointestinal upper regions as a negative controlgroup for pancreatic cancer. Furthermore, the literature does notdescribe a method for detecting a pancreatic cancer precursor lesion.

Patent Literature 4 discloses a method for detecting pancreatic canceror a pancreatic cancer precursor lesion by combining hsa-miR-1268a,hsa-miR-939-5p, and hsa-miR-642b-3p with tens of other miRNAs. Thisliterature, however, neither describes specific detection performancethereof such as accuracy, sensitivity, or specificity for pancreaticcancer nor describes cancers in organs other than the pancreas as anegative control group for pancreatic cancer.

Patent Literature 5 discloses a method for detecting pancreatic canceror a pancreatic cancer precursor lesion by combining hsa-miR-296-5p withtens of other miRNAs in blood. This literature, however, does notdescribe specific detection performance thereof such as accuracy,sensitivity, or specificity for early pancreatic cancer. In theliterature, cancers in organs other than the pancreas or benign diseaseswere not measured as a negative control group for pancreatic cancerprecursor lesions. Furthermore, the literature does not describespecific specificity.

Non-Patent Literature 5 lists hsa-miR-638, hsa-miR-3196,hsa-miR-1225-3p, and the like as miRNAs that have a larger expressionlevel in the blood of pancreatic cancer patients than that in the bloodof healthy subjects and discloses a method for detecting pancreaticcancer by combining several these miRNAs. This literature, however, doesnot describe cancers in organs other than pancreas as a negative controlgroup for pancreatic cancer.

As mentioned above, the existing tumor markers exhibit low performancein the detection of early pancreatic cancer or a pancreatic cancerprecursor lesion, or neither performance nor detection methods arespecifically shown as to the markers at a research stage. Therefore, useof these markers might require carrying out needless extra examinationdue to the false detection of healthy subjects as being early pancreaticcancer or pancreatic cancer precursor lesion patients, or might wastetherapeutic opportunity because of overlooking early pancreatic canceror pancreatic cancer precursor lesion patients. In addition, themeasurement of tens to hundreds of miRNAs increases examination costsand is therefore difficult to use in large-scale screening such asmedical checkup. Furthermore, the collection of pancreatic tissues formeasuring the tumor markers is highly invasive to patients and is notfavorable. Hence, there is a demand for a highly accurate earlypancreatic cancer or pancreatic cancer precursor lesion marker that isdetectable from blood, which can be collected in less invasive manner,and is capable of correctly determining an early pancreatic cancer orpancreatic cancer precursor lesion patient as an early pancreatic canceror pancreatic cancer precursor lesion patient and a healthy subject as ahealthy subject. Particularly, a highly sensitive early pancreaticcancer or pancreatic cancer precursor lesion marker is desired becausetumor resection based on early detection is only radical cure forpancreatic cancer.

Means for Solution of Problem

The present inventors have conducted diligent studies to attain theobject and consequently completed the present invention by identifyingseveral genes usable as markers for the detection of early pancreaticcancer or a pancreatic cancer precursor lesion from blood, which can becollected with minimal invasiveness, and finding that early pancreaticcancer or a pancreatic cancer precursor lesion can be significantlydetected by using nucleic acids capable of specifically binding to anyof these markers.

SUMMARY OF INVENTION

The present invention has the following features:

(1) A kit for the detection of early pancreatic cancer or a pancreaticcancer precursor lesion, comprising a nucleic acid(s) capable ofspecifically binding to at least one polynucleotides selected from thegroup consisting of the following early pancreatic cancer or pancreaticcancer precursor lesion markers: miR-6784-5p, miR-1181, miR-671-5p,miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675,miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-1343-5p,miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p,miR-652-5p, miR-4257, miR-6785-5p, miR-7110-5p, miR-6887-5p, miR-887-3p,miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p,miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p,miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p,miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p,miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688,miR-3917, miR-5787, miR-4632-5p, miR-6126, miR-135a-3p, miR-8063,miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p,miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p,miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920,miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p,miR-4447, miR-6869-5p, miR-6794-5p, miR-6511a-5p, miR-6824-5p,miR-6766-3p, miR-6511a-5p, and miR-6749-5p.

(2) The kit according to (1), wherein miR-6784-5p is hsa-miR-6784-5p,miR-1181 is hsa-miR-1181, miR-671-5p is hsa-miR-671-5p, miR-6857-5p ishsa-miR-6857-5p, miR-4276 is hsa-miR-4276, miR-1914-3p ishsa-miR-1914-3p, miR-149-3p is hsa-miR-149-3p, miR-937-5p ishsa-miR-937-5p, miR-4675 is hsa-miR-4675, miR-6795-5p ishsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090 ishsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p ishsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p ishsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p ishsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p ishsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p ishsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p ishsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p ishsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p ishsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p ishsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 ishsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p ishsa-miR-6732-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p ishsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 ishsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p ishsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p ishsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p ishsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p ishsa-miR-1233-5p, miR-211-3p is hsa-miR-211-3p, miR-4758-5p ishsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p,miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 ishsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p,miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 ishsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089,miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b ishsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p ishsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p ishsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6752-5p ishsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 ishsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p ishsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920,miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 ishsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p,miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p ishsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p ishsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p ishsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, and miR-6749-5p ishsa-miR-6749-5p.

(3) The kit according to (1) or (2), wherein the nucleic acid(s) is apolynucleotide(s) selected from the group consisting of the followingpolynucleotides (a) to (e):

(a) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t, a variant thereof, a derivative thereof, or afragment thereof comprising 15 or more consecutive nucleotides;(b) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250;(c) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227to 229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(d) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t; and(e) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (a) to (d).

(4) The kit according to any of (1) to (3), wherein the kit furthercomprises a nucleic acid(s) capable of specifically binding to at leastone polynucleotide selected from the group consisting of other earlypancreatic cancer or pancreatic cancer precursor lesion markersmiR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178,miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689, miR-6816-5p,miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p,miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p,miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185,miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p,miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100,miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p,miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271,miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p,miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p,miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p,miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p,miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p,miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p,miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p,miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5p,miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p, miR-6872-3p,miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534,miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p,miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b,miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p,miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p,miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p,miR-7704, miR-4749-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-4739,miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674,miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, miR-4730, miR-4286,and miR-4739.

(5) The kit according to (4), wherein miR-1908-5p is hsa-miR-1908-5p,miR-6729-5p is hsa-miR-6729-5p, miR-5195-3p is hsa-miR-5195-3p, miR-638is hsa-miR-638, miR-6125 is hsa-miR-6125, miR-3178 is hsa-miR-3178,miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-4723-5p ishsa-miR-4723-5p, miR-4746-3p is hsa-miR-4746-3p, miR-4689 ishsa-miR-4689, miR-6816-5p is hsa-miR-6816-5p, miR-6757-5p ishsa-miR-6757-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6724-5p ishsa-miR-6724-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6875-5p ishsa-miR-6875-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4508 ishsa-miR-4508, miR-6085 is hsa-miR-6085, miR-6779-5p is hsa-miR-6779-5p,miR-642a-3p is hsa-miR-642a-3p, miR-4695-5p is hsa-miR-4695-5p,miR-7847-3p is hsa-miR-7847-3p, miR-3197 is hsa-miR-3197, miR-6769b-5pis hsa-miR-6769b-5p, miR-7641 is hsa-miR-7641, miR-187-5p ishsa-miR-187-5p, miR-3185 is hsa-miR-3185, miR-2861 is hsa-miR-2861,miR-3940-5p is hsa-miR-3940-5p, miR-1203 is hsa-miR-1203, miR-615-5p ishsa-miR-615-5p, miR-4787-5p is hsa-miR-4787-5p, miR-1343-3p ishsa-miR-1343-3p, miR-6813-5p is hsa-miR-6813-5p, miR-1225-5p ishsa-miR-1225-5p, miR-602 is hsa-miR-602, miR-4488 is hsa-miR-4488,miR-125a-3p is hsa-miR-125a-3p, miR-5100 is hsa-miR-5100, miR-4294 ishsa-miR-4294, miR-1231 is hsa-miR-1231, miR-6765-3p is hsa-miR-6765-3p,miR-4442 is hsa-miR-4442, miR-718 is hsa-miR-718, miR-6780b-5p ishsa-miR-6780b-5p, miR-6090 is hsa-miR-6090, miR-6845-5p ishsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 is hsa-miR-4467,miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271, miR-4673 ishsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 is hsa-miR-1469,miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a, miR-6791-5p ishsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p ishsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p, miR-4417 ishsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p is hsa-miR-4707-3p,miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p is hsa-miR-5585-3p,miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072, miR-296-5p ishsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 is hsa-miR-4454,miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290, miR-3622a-5pis hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p, miR-675-5p ishsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 is hsa-miR-4648,miR-1268b is hsa-miR-1268b, miR-6741-5p is hsa-miR-6741-5p, miR-6893-5pis hsa-miR-6893-5p, miR-3162-5p is hsa-miR-3162-5p, miR-642b-3p ishsa-miR-642b-3p, miR-4734 is hsa-miR-4734, miR-150-3p is hsa-miR-150-3p,miR-8089 is hsa-miR-8089, miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p ishsa-miR-7113-3p, miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p ishsa-miR-6799-5p, miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p ishsa-miR-92b-5p, miR-3679-5p is hsa-miR-3679-5p, miR-4792 ishsa-miR-4792, miR-3656 is hsa-miR-3656, miR-92a-2-5p ishsa-miR-92a-2-5p, miR-4466 is hsa-miR-4466, miR-4513 is hsa-miR-4513,miR-6781-5p is hsa-miR-6781-5p, miR-4649-5p is hsa-miR-4649-5p,miR-6775-5p is hsa-miR-6775-5p, miR-4651 is hsa-miR-4651, miR-3195 ishsa-miR-3195, miR-6726-5p is hsa-miR-6726-5p, miR-6872-3p ishsa-miR-6872-3p, miR-371a-5p is hsa-miR-371a-5p, miR-6777-5p ishsa-miR-6777-5p, miR-6789-5p is hsa-miR-6789-5p, miR-7975 ishsa-miR-7975, miR-6821-5p is hsa-miR-6821-5p, miR-4534 is hsa-miR-4534,miR-619-5p is hsa-miR-619-5p, miR-7107-5p is hsa-miR-7107-5p,miR-1228-3p is hsa-miR-1228-3p, miR-6774-5p is hsa-miR-6774-5p,miR-6805-5p is hsa-miR-6805-5p, miR-23a-3p is hsa-miR-23a-3p,miR-4665-5p is hsa-miR-4665-5p, miR-4505 is hsa-miR-4505, miR-4638-5p ishsa-miR-4638-5p, miR-24-3p is hsa-miR-24-3p, miR-3135b is hsa-miR-3135b,miR-4745-5p is hsa-miR-4745-5p, miR-128-1-5p is hsa-miR-128-1-5p,miR-4476 is hsa-miR-4476, miR-4687-3p is hsa-miR-4687-3p, miR-3665 ishsa-miR-3665, miR-6806-5p is hsa-miR-6806-5p, miR-3937 is hsa-miR-3937,miR-711 is hsa-miR-711, miR-3141 is hsa-miR-3141, miR-3188 ishsa-miR-3188, miR-4281 is hsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p,miR-6880-5p is hsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 ishsa-miR-3648, miR-6721-5p is hsa-miR-6721-5p, miR-4492 is hsa-miR-4492,miR-744-5p is hsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p ishsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p,miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 ishsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p,miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 ishsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076,miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 ishsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, andmiR-4739 is hsa-miR-4739.

(6) The kit according to (4) or (5), wherein the nucleic acid(s) is apolynucleotide(s) selected from the group consisting of the followingpolynucleotides (f) to (j):

(f) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotidesequence derived from the nucleotide sequence by the replacement of uwith t, a variant thereof, a derivative thereof, or a fragment thereofcomprising 15 or more consecutive nucleotides;(g) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249;(h) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 84 to 226,230 to 245, 247, and 249 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(i) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230 to245, 247, and 249 or a nucleotide sequence derived from the nucleotidesequence by the replacement of u with t; and(j) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (f) to (i).

(7) A device for the detection of early pancreatic cancer or apancreatic cancer precursor lesion, comprising a nucleic acid(s) capableof specifically binding to at least one polynucleotide selected fromearly pancreatic cancer or pancreatic cancer precursor lesion markersmiR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p,miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090,miR-3620-5p, miR-1343-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p,miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257, miR-6785-5p,miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572,miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p,miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270,miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p,miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p,miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787,miR-4632-5p, miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089,miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p,miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131,miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448,miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p,miR-6794-5p, miR-6511a-5p, miR-6824-5p, miR-6766-3p, miR-6511a-5p, andmiR-6749-5p.

(8) The device according to (7), wherein miR-6784-5p is hsa-miR-6784-5p,miR-1181 is hsa-miR-1181, miR-671-5p is hsa-miR-671-5p, miR-6857-5p ishsa-miR-6857-5p, miR-4276 is hsa-miR-4276, miR-1914-3p ishsa-miR-1914-3p, miR-149-3p is hsa-miR-149-3p, miR-937-5p ishsa-miR-937-5p, miR-4675 is hsa-miR-4675, miR-6795-5p ishsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090 ishsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p ishsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p ishsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p ishsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p ishsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p ishsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p ishsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p ishsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p ishsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p ishsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 ishsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p ishsa-miR-6732-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p ishsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 ishsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p ishsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p ishsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p ishsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p ishsa-miR-1233-5p, miR-211-3p is hsa-miR-211-3p, miR-4758-5p ishsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p,miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 ishsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p,miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 ishsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089,miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b ishsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p ishsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p ishsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6752-5p ishsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 ishsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p ishsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920,miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 ishsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p,miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p ishsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p ishsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p ishsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, and miR-6749-5p ishsa-miR-6749-5p.

(9) The device according to (7) or (8), wherein the nucleic acid(s) is apolynucleotide(s) selected from the group consisting of the followingpolynucleotides (a) to (e):

(a) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t, a variant thereof, a derivative thereof, or afragment thereof comprising 15 or more consecutive nucleotides;(b) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 1 to 83, 227 to 229, 246, 248 and 250;(c) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227to 229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(d) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t; and(e) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (a) to (d).

(10) The device according to any of (7) to (9), wherein the devicefurther comprises a nucleic acid(s) capable of specifically binding toat least one polynucleotide selected from the group consisting of otherearly pancreatic cancer or pancreatic cancer precursor lesion markersmiR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125, miR-3178,miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689, miR-6816-5p,miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p, miR-6875-5p,miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p, miR-4695-5p,miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p, miR-3185,miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p, miR-1343-3p,miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p, miR-5100,miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718, miR-6780b-5p,miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p, miR-4271,miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a, miR-6791-5p,miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449, miR-4707-3p,miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p, miR-204-3p,miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p, miR-675-5p,miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p, miR-3162-5p,miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p, miR-7113-3p,miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p, miR-3679-5p,miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513, miR-6781-5p,miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p, miR-6872-3p,miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975, miR-6821-5p, miR-4534,miR-619-5p, miR-7107-5p, miR-1228-3p, miR-6774-5p, miR-6805-5p,miR-23a-3p, miR-4665-5p, miR-4505, miR-4638-5p, miR-24-3p, miR-3135b,miR-4745-5p, miR-128-1-5p, miR-4476, miR-4687-3p, miR-3665, miR-6806-5p,miR-3937, miR-711, miR-3141, miR-3188, miR-4281, miR-5196-5p,miR-6880-5p, miR-3960, miR-3648, miR-6721-5p, miR-4492, miR-744-5p,miR-7704, miR-4749-5p, miR-762, miR-6836-3p, miR-6727-5p, miR-4739,miR-7977, miR-4484, miR-6515-3p, miR-373-5p, miR-4258, miR-4674,miR-3180, miR-6076, miR-1238-5p, miR-4463, miR-4486, miR-4730, miR-4286,and miR-4739.

(11) The device according to (10), wherein miR-1908-5p ishsa-miR-1908-5p, miR-6729-5p is hsa-miR-6729-5p, miR-5195-3p ishsa-miR-5195-3p, miR-638 is hsa-miR-638, miR-6125 is hsa-miR-6125,miR-3178 is hsa-miR-3178, miR-3196 is hsa-miR-3196, miR-8069 ishsa-miR-8069, miR-4723-5p is hsa-miR-4723-5p, miR-4746-3p ishsa-miR-4746-3p, miR-4689 is hsa-miR-4689, miR-6816-5p ishsa-miR-6816-5p, miR-6757-5p is hsa-miR-6757-5p, miR-7109-5p ishsa-miR-7109-5p, miR-6724-5p is hsa-miR-6724-5p, miR-1225-3p ishsa-miR-1225-3p, miR-6875-5p is hsa-miR-6875-5p, miR-7108-5p ishsa-miR-7108-5p, miR-4508 is hsa-miR-4508, miR-6085 is hsa-miR-6085,miR-6779-5p is hsa-miR-6779-5p, miR-642a-3p is hsa-miR-642a-3p,miR-4695-5p is hsa-miR-4695-5p, miR-7847-3p is hsa-miR-7847-3p, miR-3197is hsa-miR-3197, miR-6769b-5p is hsa-miR-6769b-5p, miR-7641 ishsa-miR-7641, miR-187-5p is hsa-miR-187-5p, miR-3185 is hsa-miR-3185,miR-2861 is hsa-miR-2861, miR-3940-5p is hsa-miR-3940-5p, miR-1203 ishsa-miR-1203, miR-615-5p is hsa-miR-615-5p, miR-4787-5p ishsa-miR-4787-5p, miR-1343-3p is hsa-miR-1343-3p, miR-6813-5p ishsa-miR-6813-5p, miR-1225-5p is hsa-miR-1225-5p, miR-602 is hsa-miR-602,miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-5100 ishsa-miR-5100, miR-4294 is hsa-miR-4294, miR-1231 is hsa-miR-1231,miR-6765-3p is hsa-miR-6765-3p, miR-4442 is hsa-miR-4442, miR-718 ishsa-miR-718, miR-6780b-5p is hsa-miR-6780b-5p, miR-6090 is hsa-miR-6090,miR-6845-5p is hsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 ishsa-miR-4467, miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271,miR-4673 is hsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 ishsa-miR-1469, miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a,miR-6791-5p is hsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p,miR-4433b-3p is hsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p,miR-4417 is hsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p ishsa-miR-4707-3p, miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p ishsa-miR-5585-3p, miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072,miR-296-5p is hsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 ishsa-miR-4454, miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290,miR-3622a-5p is hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p,miR-675-5p is hsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 ishsa-miR-4648, miR-1268b is hsa-miR-1268b, miR-6741-5p ishsa-miR-6741-5p, miR-6893-5p is hsa-miR-6893-5p, miR-3162-5p ishsa-miR-3162-5p, miR-642b-3p is hsa-miR-642b-3p, miR-4734 ishsa-miR-4734, miR-150-3p is hsa-miR-150-3p, miR-8089 is hsa-miR-8089,miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p is hsa-miR-7113-3p,miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p is hsa-miR-6799-5p,miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p is hsa-miR-92b-5p,miR-3679-5p is hsa-miR-3679-5p, miR-4792 is hsa-miR-4792, miR-3656 ishsa-miR-3656, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4466 ishsa-miR-4466, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p,miR-4649-5p is hsa-miR-4649-5p, miR-6775-5p is hsa-miR-6775-5p, miR-4651is hsa-miR-4651, miR-3195 is hsa-miR-3195, miR-6726-5p ishsa-miR-6726-5p, miR-6872-3p is hsa-miR-6872-3p, miR-371a-5p ishsa-miR-371a-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6789-5p ishsa-miR-6789-5p, miR-7975 is hsa-miR-7975, miR-6821-5p ishsa-miR-6821-5p, miR-4534 is hsa-miR-4534, miR-619-5p is hsa-miR-619-5p,miR-7107-5p is hsa-miR-7107-5p, miR-1228-3p is hsa-miR-1228-3p,miR-6774-5p is hsa-miR-6774-5p, miR-6805-5p is hsa-miR-6805-5p,miR-23a-3p is hsa-miR-23a-3p, miR-4665-5p is hsa-miR-4665-5p, miR-4505is hsa-miR-4505, miR-4638-5p is hsa-miR-4638-5p, miR-24-3p ishsa-miR-24-3p, miR-3135b is hsa-miR-3135b, miR-4745-5p ishsa-miR-4745-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-4476 ishsa-miR-4476, miR-4687-3p is hsa-miR-4687-3p, miR-3665 is hsa-miR-3665,miR-6806-5p is hsa-miR-6806-5p, miR-3937 is hsa-miR-3937, miR-711 ishsa-miR-711, miR-3141 is hsa-miR-3141, miR-3188 is hsa-miR-3188,miR-4281 is hsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p, miR-6880-5p ishsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 is hsa-miR-3648,miR-6721-5p is hsa-miR-6721-5p, miR-4492 is hsa-miR-4492, miR-744-5p ishsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p ishsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p,miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 ishsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p,miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 ishsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076,miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 ishsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, andmiR-4739 is hsa-miR-4739.

(12) The device according to (10) or (11), wherein the nucleic acid(s)is a polynucleotide(s) selected from the group consisting of thefollowing polynucleotides (f) to (j):

(f) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotidesequence derived from the nucleotide sequence by the replacement of uwith t, a variant thereof, a derivative thereof, or a fragment thereofcomprising 15 or more consecutive nucleotides;(g) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249;(h) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 84 to 226,230 to 245, 247, and 249 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(i) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230 to245, 247, and 249 or a nucleotide sequence derived from the nucleotidesequence by the replacement of u with t; and(j) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (f) to (i).

(13) The device according to any one of (7) to (12), wherein the deviceis for measurement based on a hybridization technique.

(14) The device according to (13), wherein the hybridization techniqueis a nucleic acid array technique.

(15) A method for detecting early pancreatic cancer or a pancreaticcancer precursor lesion in a subject, comprising: measuring anexpression level(s) of a target nucleic acid(s) in a sample from thesubject using a kit according to any of (1) to (6) or a device accordingto any of (7) to (14); and evaluating in vitro whether or not thesubject has early pancreatic cancer or a pancreatic cancer precursorlesion using both of the measured expression level(s) and a controlexpression level(s) in a sample from a healthy subject measured in thesame way, to detect the presence or absence of early pancreatic canceror a pancreatic cancer precursor lesion in the subject.

(16) A method for detecting early pancreatic cancer or a pancreaticcancer precursor lesion in a subject, comprising: measuring anexpression level(s) of a target gene(s) in a sample from the subjectusing a kit according to any of (1) to (6) or a device according to anyof (7) to (14); and assigning the expression level(s) of the targetgene(s) in the sample from the subject to a discriminant (discriminantfunction) to evaluate the presence or absence of early pancreatic canceror a pancreatic cancer precursor lesion, wherein the discriminant isprepared with the gene expression level(s) in a sample(s) from asubject(s) known to have early pancreatic cancer or a pancreatic cancerprecursor lesion and the gene expression level(s) in a sample(s) from ahealthy subject(s) as supervising samples and is capable ofdiscriminating an early pancreatic cancer or pancreatic cancer precursorlesion patient from a healthy subject.

(17) The method according to (15) or (16), wherein the subject is ahuman.

(18) The method according to any one of (15) to (17), wherein the sampleis blood, serum, or plasma.

Definition of Terms

The terms used herein are defined as described below.

The term “pancreatic cancer” used herein refers to invasive ductalcarcinomas. Specifically, the “pancreatic cancer” includes papillaryadenocarcinoma, tubular adenocarcinoma, poorly differentiatedadenocarcinoma, adenosquamous carcinoma, mucinous carcinoma, anaplasticcarcinoma, and the like formed in the pancreas (“Classification ofPancreatic Carcinoma”, the 6th edition, revised version, 2013, JapanPancreas Society, KANEHARA & Co., LTD. (Tokyo, Japan), p. 27-28).

The term “pancreatic cancer precursor lesion” used herein refers toexocrine neoplasms formed in the pancreas. Specifically, the “pancreaticcancer precursor lesion” includes serous cystic neoplasms (SCNs), serouscystadenoma (SCA), serous cystadenocarcinoma (SCC), mucinous cysticneoplasms (MCNs), mucinous cystadenoma (MCA), mucinouscystadenocarcinoma (MCC), intraductal papillary-mucinous neoplasms(IPMNs), intraductal papillary-mucinous adenoma (IPMA), intraductalpapillary-mucinous carcinoma (IPMC), and the like (“General Rules forthe Study of Pancreatic Cancer”, the 6th edition, revised version, 2013,Japan Pancreas Society, KANEHARA & Co., LTD. (Tokyo, Japan), p. 24-27).

The term “stage of progression of pancreatic cancer” used herein isclassified into stages 0, IA, IB, IIA, IIB, III, IVa, and IVb accordingto the local extent of the primary tumor, lymph node metastasis, distantmetastasis, etc. (“General Rules for the Study of Pancreatic Cancer”,the 6th edition, revised version, 2013, Japan Pancreas Society, KANEHARA& Co., LTD. (Tokyo, Japan), p. 55-57).

The term “early pancreatic cancer” used herein refers to pancreaticcancer of stage 0, IA, IB, IIA, or IIB.

The term “advanced pancreatic cancer” used herein refers to pancreaticcancer of stage III, IVa, or IVb.

The term “benign disease” used herein refers to a disease with anonmalignant tumor in an organ.

Abbreviations or terms such as “nucleotide”, “polynucleotide”, “DNA”,and “RNA” used herein abide by “Guidelines for the preparation ofspecification which contains nucleotide and/or amino acid sequences”(edited by Japan Patent Office) and common use in the art.

The term “polynucleotide” used herein refers to a nucleic acid includingany of RNA, DNA, and RNA/DNA (chimera). The DNA includes any of cDNA,genomic DNA, and synthetic DNA. The RNA includes any of total RNA, mRNA,rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA and synthetic RNA.Here the “synthetic DNA” and the “synthetic RNA” refer to a DNA and anRNA artificially prepared using, for example, an automatic nucleic acidsynthesizer, on the basis of predetermined nucleotide sequences (whichmay be any of natural and non-natural sequences). Herein, the“non-natural sequence” is intended to be used in a broad sense andincludes, for example, a sequence comprising substitution, deletion,insertion, and/or addition of one or more nucleotides (i.e., a variantsequence) and a sequence comprising one or more modified nucleotides(i.e., a modified sequence), which are different from the naturalsequence. Herein, the term “polynucleotide” is used interchangeably withthe term “nucleic acid.”

The term “fragment” used herein is a polynucleotide having a nucleotidesequence that consists of a consecutive portion of a polynucleotide anddesirably has a length of 15 or more nucleotides, preferably 17 or morenucleotides, more preferably 19 or more nucleotides.

The term “gene” used herein is intended to include not only RNA anddouble-stranded DNA but also each single-stranded DNA such as a plus(+)strand (or a sense strand) or a complementary strand (or an antisensestrand) constituting the duplex. The gene is not particularly limited byits length.

Thus, the “gene” used herein includes any of double-stranded DNAincluding human genomic DNA, single-stranded DNA (plus strand),single-stranded DNA having a sequence complementary to the plus strand(complementary strand) (e.g., cDNA), microRNA (miRNA), and theirfragments, and their transcripts, unless otherwise specified. The “gene”includes not only a “gene” represented by a particular nucleotidesequence (or SEQ ID NO) but “nucleic acids” encoding RNAs havingbiological functions equivalent to RNA encoded by the gene, for example,a congener (i.e., a homolog or an ortholog), a variant (e.g., a geneticpolymorph), and a derivative. Specific examples of such a “nucleic acid”encoding a congener, a variant, or a derivative can include a “nucleicacid” having a nucleotide sequence hybridizing under stringentconditions described later to a complementary sequence of a nucleotidesequence represented by any of SEQ ID NOs: 1 to 812 or a nucleotidesequence derived from the nucleotide sequence by the replacement of uwith t. Regardless whether or not there is a difference in functionalregion, the “gene” can comprise, for example, expression controlregions, coding region, exons, or introns. The “gene” may be containedin a cell or may exist alone after being released from a cell.Alternatively, the “gene” may be in a state enclosed in a vesicle calledexosome.

The term “exosome” used herein refers to a vesicle that is encapsulatedby lipid bilayer and secreted from a cell. The exosome is derived from amultivesicular endosome and may incorporate biomaterials such as “genes”(e.g., RNA or DNA) or proteins when released into an extracellularenvironment. The exosome is known to be contained in a body fluid suchas blood, serum, plasma, or lymph.

The term “transcript” used herein refers to an RNA synthesized from theDNA sequence of a gene as a template. RNA polymerase binds to a sitecalled promoter located upstream of the gene and adds ribonucleotidescomplementary to the nucleotide sequence of the DNA to the 3′ end tosynthesize an RNA. This RNA contains not only the gene itself but thewhole sequence from a transcription initiation site to the end of apolyA sequence, including expression control regions, coding region,exons, or introns.

Unless otherwise specified, the term “microRNA (miRNA)” used herein isintended to mean a 15- to 25-nucleotide non-coding RNA that istranscribed as an RNA precursor having a hairpin-like structure, cleavedby a dsRNA-cleaving enzyme having RNase III cleavage activity, andintegrated into a protein complex called RISC, and that is involved inthe suppression of translation of mRNA. The term “miRNA” used hereinincludes not only a “miRNA” represented by a particular nucleotidesequence (or SEQ ID NO) but a precursor of the “miRNA” (pre-miRNA orpri-miRNA), and miRNAs having biological functions equivalent thereto,for example, a congener (i.e., a homolog or an ortholog), a variant(e.g., a genetic polymorph), and a derivative. Such a precursor, acongener, a variant, or a derivative can be specifically identifiedusing miRBase Release 20 (http://www.mirbase.org/), and examples thereofcan include a “miRNA” having a nucleotide sequence hybridizing understringent conditions described later to a complementary sequence of anyparticular nucleotide sequence represented by any of SEQ ID NOs: 1 to812. The term “miRNA” used herein may be a gene product of a miR gene.Such a gene product includes a mature miRNA (e.g., a 15- to25-nucleotide or 19- to 25-nucleotide non-coding RNA involved in thesuppression of translation of mRNA as described above) or a miRNAprecursor (e.g., pre-miRNA or pri-miRNA as described above).

The term “probe” used herein includes a polynucleotide that is used forspecifically detecting an RNA resulting from the expression of a gene ora polynucleotide derived from the RNA, and/or a polynucleotidecomplementary thereto.

The term “primer” used herein includes a polynucleotide thatspecifically recognizes and amplifies an RNA resulting from theexpression of a gene or a polynucleotide derived from the RNA, and/or apolynucleotide complementary thereto.

In this context, the complementary polynucleotide (complementary strandor reverse strand) means a polynucleotide in a complementaryrelationship based on A:T (U) and G:C base pairs with the full-lengthsequence of a polynucleotide consisting of a nucleotide sequence definedby any of SEQ ID NOs: 1 to 812 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, or a partialsequence thereof (here, this full-length or partial sequence is referredto as a plus strand for the sake of convenience). The phrase“polynucleotide consisting of a nucleotide sequence complementary” to anucleotide sequence represented by any of SEQ ID NOs: 1 to 812 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t is also basically understood in the same way.

The term “stringent conditions” used herein refers to conditions underwhich a nucleic acid probe hybridizes to its target sequence to adetectably larger extent (e.g., a measurement value equal to or largerthan “(a mean of background measurement values)+(a standard error of thebackground measurement values)×2”) than that for other sequences. Thestringent conditions are dependent on a sequence and differ depending onan environment where hybridization is performed. A target sequencecomplementary in 100% to the nucleic acid probe can be identified bycontrolling the stringency of hybridization and/or washing conditions.Specific examples of the “stringent conditions” will be mentioned later.

The term “Tm value” used herein means a temperature at which thedouble-stranded part of a polynucleotide is denatured into singlestrands so that the double strands and the single strands exist at aratio of 1:1.

The term “variant” used herein means, in the case of a nucleic acid, anatural variant attributed to polymorphism, mutation, or the like; avariant containing the deletion, substitution, addition, or insertion of1 or 2 or more (e.g., 1 to several) nucleotides in a nucleotide sequencerepresented by any of SEQ ID NOs: 1 to 812 or a nucleotide sequencederived from the nucleotide sequence by the replacement of u with t, ora partial sequence thereof; a variant that exhibits percent (%) identityof approximately 90% or higher, approximately 95% or higher,approximately 97% or higher, approximately 98% or higher, approximately99% or higher to each of these nucleotide sequences or the partialsequences thereof; or a nucleic acid hybridizing under the stringentconditions defined above to a polynucleotide or an oligonucleotidecomprising each of these nucleotide sequences or the partial sequencesthereof.

The term “several” used herein means an integer of approximately 10, 9,8, 7, 6, 5, 4, 3, or 2.

The variant as used herein can be prepared by use of a well-knowntechnique such as site-directed mutagenesis or mutagenesis using PCR.

The term “percent (%) identity” used herein can be determined with orwithout an introduced gap, using a protein or gene search system basedon BLAST or FASTA (Zheng Zhang et al., 2000, J. Comput. Biol., Vol. 7,p. 203-214; Altschul, S. F. et al., 1990, Journal of Molecular Biology,Vol. 215, p. 403-410; and Pearson, W. R. et al., 1988, Proc. Natl. Acad.Sci. U.S.A., Vol. 85, p. 2444-2448).

The term “derivative” used herein is meant to include a modified nucleicacid, for example, unlimitedly, a derivative labeled with a fluorophoreor the like, a derivative containing a modified nucleotide (e.g., anucleotide containing a group such as halogen, alkyl such as methyl,alkoxy such as methoxy, thio, or carboxymethyl, and a nucleotide thathas undergone base rearrangement, double bond saturation, deamination,replacement of an oxygen molecule with a sulfur atom, etc.), PNA(peptide nucleic acid; Nielsen, P. E. et al., 1991, Science, Vol. 254,p. 1497-500), and LNA (locked nucleic acid; Obika, S. et al., 1998,Tetrahedron Lett., Vol. 39, p. 5401-5404).

As used herein, the “nucleic acid” capable of specifically binding to apolynucleotide selected from the early pancreatic cancer or pancreaticcancer precursor lesion marker miRNAs described above is a synthesizedor prepared nucleic acid and specifically includes a “nucleic acidprobe” or a “primer”. The “nucleic acid” is utilized directly orindirectly for detecting the presence or absence of early pancreaticcancer or a pancreatic cancer precursor lesion in a subject, fordiagnosing the presence or absence or the severity of early pancreaticcancer or a pancreatic cancer precursor lesion, the presence or absenceor the degree of amelioration of early pancreatic cancer or a pancreaticcancer precursor lesion, or the therapeutic sensitivity of earlypancreatic cancer or a pancreatic cancer precursor lesion, or forscreening for a candidate substance useful in the prevention,amelioration, or treatment of early pancreatic cancer or a pancreaticcancer precursor lesion. The “nucleic acid” includes a nucleotide, anoligonucleotide, and a polynucleotide capable of specificallyrecognizing and binding to a transcript represented by any of SEQ IDNOs: 1 to 812 or a synthetic cDNA nucleic acid thereof in vivo,particularly in a sample such as a body fluid (e.g., blood or urine), inrelation to the development of early pancreatic cancer or a pancreaticcancer precursor lesion. The nucleotide, the oligonucleotide, and thepolynucleotide can be effectively used as probes for detecting theaforementioned gene expressed in vivo, in tissues, in cells, or the likeon the basis of the properties described above, or as primers foramplifying the aforementioned gene expressed in vivo.

The term “detection” used herein is interchangeable with the term“examination”, “measurement”, “decision”, or “decision support”. As usedherein, the term “evaluation” is meant to include diagnosing orevaluation-supporting on the basis of examination results or measurementresults.

The term “subject” used herein means a mammal such as a primateincluding a human and a chimpanzee, a pet animal including a dog and acat, a livestock animal including cattle, a horse, sheep, and a goat, arodent including a mouse and a rat, and an animal that is kept in a zoo.The subject is preferably a human. The term “healthy subject” also meanssuch a mammal without being affected with the cancer to be detected. Thehealthy subject is preferably a human.

The term “P” or “P value” used herein refers to a probability at which amore extreme statistic than that actually calculated from data undernull hypothesis is observed in a statistical test. Thus, with smaller“P” or “P value”, it is regarded that there is a more significantdifference between subjects to be compared.

The term “sensitivity” used herein means a value of (the number of truepositives)/(the number of true positives+the number of false negatives).High sensitivity allows early pancreatic cancer or a pancreatic cancerprecursor lesion to be detected early, leading to the complete resectionof cancer sites and reduction in the rate of recurrence.

The term “specificity” used herein means a value of (the number of truenegatives)/(the number of true negatives+the number of false positives).High specificity prevents needless extra examination for healthysubjects misjudged as being early pancreatic cancer or pancreatic cancerprecursor lesion patients, leading to reduction in burden on patientsand reduction in medical expense.

The term “accuracy” used herein means a value of (the number of truepositives+the number of true negatives)/(the total number of cases). Theaccuracy indicates the ratio of samples that are identified correctly toall samples, and serves as a primary index for evaluating detectionperformance.

As used herein, the “sample” that is subject to determination,detection, or diagnosis refers to a tissue and a biological material inwhich the expression of the gene of the present invention varies asearly pancreatic cancer or pancreatic cancer precursor lesion develops,as early pancreatic cancer or pancreatic cancer precursor lesionprogresses, or as therapeutic effects on early pancreatic cancer or apancreatic cancer precursor lesion are exerted. Specifically, the“sample” refers to a pancreatic tissue, a peripancreatic vascularchannel, lymph node, and organ, an organ suspected of having metastasis,the skin, a body fluid such as blood, urine, saliva, sweat, or tissueexudates, serum or plasma prepared from blood, feces, hair, and thelike. The “sample” further refers to a biological sample extractedtherefrom, specifically, a gene such as RNA or miRNA.

The term “hsa-miR-6784-5p gene” or “hsa-miR-6784-5p” used hereinincludes the hsa-miR-6784-5p gene (miRBase Accession No. MIMAT0027468)shown in SEQ ID NO: 1, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6784” (miRBase Accession No. MI0022629, SEQ ID NO: 251)having a hairpin-like structure is known as a precursor of“hsa-miR-6784-5p”.

The term “hsa-miR-1181 gene” or “hsa-miR-1181” used herein includes thehsa-miR-1181 gene (miRBase Accession No. MIMAT0005826) shown in SEQ IDNO: 2, a homolog or an ortholog thereof of a different organism species,and the like. The gene can be obtained by a method described inSubramanian S et al., 2008, Oncogene, Vol. 27, p. 2015-2026. Also,“hsa-mir-1181” (miRBase Accession No. MI0006274, SEQ ID NO: 252) havinga hairpin-like structure is known as a precursor of “hsa-miR-1181”.

The term “hsa-miR-671-5p gene” or “hsa-miR-671-5p” used herein includesthe hsa-miR-671-5p gene (miRBase Accession No. MIMAT0003880) shown inSEQ ID NO: 3, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inBerezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also,“hsa-mir-671” (miRBase Accession No. MI0003760, SEQ ID NO: 253) having ahairpin-like structure is known as a precursor of “hsa-miR-671-5p”.

The term “hsa-miR-6857-5p gene” or “hsa-miR-6857-5p” used hereinincludes the hsa-miR-6857-5p gene (miRBase Accession No. MIMAT0027614)shown in SEQ ID NO: 4, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6857” (miRBase Accession No. MI0022703, SEQ ID NO: 254)having a hairpin-like structure is known as a precursor of“hsa-miR-6857-5p”.

The term “hsa-miR-4276 gene” or “hsa-miR-4276” used herein includes thehsa-miR-4276 gene (miRBase Accession No. MIMAT0016904) shown in SEQ IDNO: 5, a homolog or an ortholog thereof of a different organism species,and the like. The gene can be obtained by a method described in Goff L Aet al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4276” (miRBaseAccession No. MI0015882, SEQ ID NO: 255) having a hairpin-like structureis known as a precursor of “hsa-miR-4276”.

The term “hsa-miR-1914-3p gene” or “hsa-miR-1914-3p” used hereinincludes the hsa-miR-1914-3p gene (miRBase Accession No. MIMAT0007890)shown in SEQ ID NO: 6, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505.Also, “hsa-mir-1914” (miRBase Accession No. MI0008335, SEQ ID NO: 256)having a hairpin-like structure is known as a precursor of“hsa-miR-1914-3p”.

The term “hsa-miR-149-3p gene” or “hsa-miR-149-3p” used herein includesthe hsa-miR-149-3p gene (miRBase Accession No. MIMAT0004609) shown inSEQ ID NO: 7, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also,“hsa-mir-149” (miRBase Accession No. MI0000478, SEQ ID NO: 257) having ahairpin-like structure is known as a precursor of “hsa-miR-149-3p”.

The term “hsa-miR-937-5p gene” or “hsa-miR-937-5p” used herein includesthe hsa-miR-937-5p gene (miRBase Accession No. MIMAT0022938) shown inSEQ ID NO: 8, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLui W O et al., 2007, Cancer Res, Vol. 67, p. 6031-6043. Also,“hsa-mir-937” (miRBase Accession No. MI0005759, SEQ ID NO: 258) having ahairpin-like structure is known as a precursor of “hsa-miR-937-5p”.

The term “hsa-miR-4675 gene” or “hsa-miR-4675” used herein includes thehsa-miR-4675 gene (miRBase Accession No. MIMAT0019757) shown in SEQ IDNO: 9, a homolog or an ortholog thereof of a different organism species,and the like. The gene can be obtained by a method described in PerssonH et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also, “hsa-mir-4675”(miRBase Accession No. MI0017306, SEQ ID NO: 259) having a hairpin-likestructure is known as a precursor of “hsa-miR-4675”.

The term “hsa-miR-6795-5p gene” or “hsa-miR-6795-5p” used hereinincludes the hsa-miR-6795-5p gene (miRBase Accession No. MIMAT0027490)shown in SEQ ID NO: 10, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6795” (miRBase Accession No. MI0022640, SEQ ID NO: 260)having a hairpin-like structure is known as a precursor of“hsa-miR-6795-5p”.

The term “hsa-miR-4731-5p gene” or “hsa-miR-4731-5p” used hereinincludes the hsa-miR-4731-5p gene (miRBase Accession No. MIMAT0019853)shown in SEQ ID NO: 11, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4731” (miRBase Accession No. MI0017368, SEQ ID NO: 261)having a hairpin-like structure is known as a precursor of“hsa-miR-4731-5p”.

The term “hsa-miR-5090 gene” or “hsa-miR-5090” used herein includes thehsa-miR-5090 gene (miRBase Accession No. MIMAT0021082) shown in SEQ IDNO: 12, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inDing N et al., 2011, J Radiat Res, Vol. 52, p. 425-432. Also,“hsa-mir-5090” (miRBase Accession No. MI0017979, SEQ ID NO: 262) havinga hairpin-like structure is known as a precursor of “hsa-miR-5090”.

The term “hsa-miR-3620-5p gene” or “hsa-miR-3620-5p” used hereinincludes the hsa-miR-3620-5p gene (miRBase Accession No. MIMAT0022967)shown in SEQ ID NO: 13, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also,“hsa-mir-3620” (miRBase Accession No. MI0016011, SEQ ID NO: 263) havinga hairpin-like structure is known as a precursor of “hsa-miR-3620-5p”.

The term “hsa-miR-1343-5p gene” or “hsa-miR-1343-5p” used hereinincludes the hsa-miR-1343-5p gene (miRBase Accession No. MIMAT0027038)shown in SEQ ID NO: 14, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-1343” (miRBase Accession No. MI0017320, SEQ ID NO: 264)having a hairpin-like structure is known as a precursor of“hsa-miR-1343-5p”.

The term “hsa-miR-6717-5p gene” or “hsa-miR-6717-5p” used hereinincludes the hsa-miR-6717-5p gene (miRBase Accession No. MIMAT0025846)shown in SEQ ID NO: 15, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also,“hsa-mir-6717” (miRBase Accession No. MI0022551, SEQ ID NO: 265) havinga hairpin-like structure is known as a precursor of “hsa-miR-6717-5p”.

The term “hsa-miR-6825-5p gene” or “hsa-miR-6825-5p” used hereinincludes the hsa-miR-6825-5p gene (miRBase Accession No. MIMAT0027550)shown in SEQ ID NO: 16, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6825” (miRBase Accession No. MI0022670, SEQ ID NO: 266)having a hairpin-like structure is known as a precursor of“hsa-miR-6825-5p”.

The term “hsa-miR-6738-5p gene” or “hsa-miR-6738-5p” used hereinincludes the hsa-miR-6738-5p gene (miRBase Accession No. MIMAT0027377)shown in SEQ ID NO: 17, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6738” (miRBase Accession No. MI0022583, SEQ ID NO: 267)having a hairpin-like structure is known as a precursor of“hsa-miR-6738-5p”.

The term “hsa-miR-6769a-5p gene” or “hsa-miR-6769a-5p” used hereinincludes the hsa-miR-6769a-5p gene (miRBase Accession No. MIMAT0027438)shown in SEQ ID NO: 18, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6769a” (miRBase Accession No. MI0022614, SEQ ID NO: 268)having a hairpin-like structure is known as a precursor of“hsa-miR-6769a-5p”.

The term “hsa-miR-4728-5p gene” or “hsa-miR-4728-5p” used hereinincludes the hsa-miR-4728-5p gene (miRBase Accession No. MIMAT0019849)shown in SEQ ID NO: 19, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4728” (miRBase Accession No. MI0017365, SEQ ID NO: 269)having a hairpin-like structure is known as a precursor of“hsa-miR-4728-5p”.

The term “hsa-miR-652-5p gene” or “hsa-miR-652-5p” used herein includesthe hsa-miR-652-5p gene (miRBase Accession No. MIMAT0022709) shown inSEQ ID NO: 20, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-652” (miRBase Accession No. MI0003667, SEQ IDNO: 270) having a hairpin-like structure is known as a precursor of“hsa-miR-652-5p”.

The term “hsa-miR-4257 gene” or “hsa-miR-4257” used herein includes thehsa-miR-4257 gene (miRBase Accession No. MIMAT0016878) shown in SEQ IDNO: 21, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4257”(miRBase Accession No. MI0015856, SEQ ID NO: 271) having a hairpin-likestructure is known as a precursor of “hsa-miR-4257”.

The term “hsa-miR-6785-5p gene” or “hsa-miR-6785-5p” used hereinincludes the hsa-miR-6785-5p gene (miRBase Accession No. MIMAT0027470)shown in SEQ ID NO: 22, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6785” (miRBase Accession No. MI0022630, SEQ ID NO: 272)having a hairpin-like structure is known as a precursor of“hsa-miR-6785-5p”.

The term “hsa-miR-7110-5p gene” or “hsa-miR-7110-5p” used hereinincludes the hsa-miR-7110-5p gene (miRBase Accession No. MIMAT0028117)shown in SEQ ID NO: 23, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-7110” (miRBase Accession No. MI0022961, SEQ ID NO: 273)having a hairpin-like structure is known as a precursor of“hsa-miR-7110-5p”.

The term “hsa-miR-6887-5p gene” or “hsa-miR-6887-5p” used hereinincludes the hsa-miR-6887-5p gene (miRBase Accession No. MIMAT0027674)shown in SEQ ID NO: 24, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6887” (miRBase Accession No. MI0022734, SEQ ID NO: 274)having a hairpin-like structure is known as a precursor of“hsa-miR-6887-5p”.

The term “hsa-miR-887-3p gene” or “hsa-miR-887-3p” used herein includesthe hsa-miR-887-3p gene (miRBase Accession No. MIMAT0004951) shown inSEQ ID NO: 25, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inBerezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also,“hsa-mir-887” (miRBase Accession No. MI0005562, SEQ ID NO: 275) having ahairpin-like structure is known as a precursor of “hsa-miR-887-3p”.

The term “hsa-miR-1228-5p gene” or “hsa-miR-1228-5p” used hereinincludes the hsa-miR-1228-5p gene (miRBase Accession No. MIMAT0005582)shown in SEQ ID NO: 26, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1228” (miRBase Accession No. MI0006318, SEQ ID NO: 276)having a hairpin-like structure is known as a precursor of“hsa-miR-1228-5p”.

The term “hsa-miR-5572 gene” or “hsa-miR-5572” used herein includes thehsa-miR-5572 gene (miRBase Accession No. MIMAT0022260) shown in SEQ IDNO: 27, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inTandon M et al., 2012, Oral Dis, Vol. 18, p. 127-131. Also,“hsa-mir-5572” (miRBase Accession No. MI0019117, SEQ ID NO: 277) havinga hairpin-like structure is known as a precursor of “hsa-miR-5572”.

The term “hsa-miR-6782-5p gene” or “hsa-miR-6782-5p” used hereinincludes the hsa-miR-6782-5p gene (miRBase Accession No. MIMAT0027464)shown in SEQ ID NO: 28, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6782” (miRBase Accession No. MI0022627, SEQ ID NO: 278)having a hairpin-like structure is known as a precursor of“hsa-miR-6782-5p”.

The term “hsa-miR-4298 gene” or “hsa-miR-4298” used herein includes thehsa-miR-4298 gene (miRBase Accession No. MIMAT0016852) shown in SEQ IDNO: 29, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4298”(miRBase Accession No. MI0015830, SEQ ID NO: 279) having a hairpin-likestructure is known as a precursor of “hsa-miR-4298”.

The term “hsa-miR-6786-5p gene” or “hsa-miR-6786-5p” used hereinincludes the hsa-miR-6786-5p gene (miRBase Accession No. MIMAT0027472)shown in SEQ ID NO: 30, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6786” (miRBase Accession No. MI0022631, SEQ ID NO: 280)having a hairpin-like structure is known as a precursor of“hsa-miR-6786-5p”.

The term “hsa-miR-5010-5p gene” or “hsa-miR-5010-5p” used hereinincludes the hsa-miR-5010-5p gene (miRBase Accession No. MIMAT0021043)shown in SEQ ID NO: 31, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Hansen T B et al., 2011, RNA Biol, Vol. 8, p. 378-383.Also, “hsa-mir-5010” (miRBase Accession No. MI0017878, SEQ ID NO: 281)having a hairpin-like structure is known as a precursor of“hsa-miR-5010-5p”.

The term “hsa-miR-6087 gene” or “hsa-miR-6087” used herein includes thehsa-miR-6087 gene (miRBase Accession No. MIMAT0023712) shown in SEQ IDNO: 32, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inYoo J K et al., 2012, Stem Cells Dev, Vol. 21, p. 2049-2057. Also,“hsa-mir-6087” (miRBase Accession No. MI0020364, SEQ ID NO: 282) havinga hairpin-like structure is known as a precursor of “hsa-miR-6087”.

The term “hsa-miR-6765-5p gene” or “hsa-miR-6765-5p” used hereinincludes the hsa-miR-6765-5p gene (miRBase Accession No. MIMAT0027430)shown in SEQ ID NO: 33, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6765” (miRBase Accession No. MI0022610, SEQ ID NO: 283)having a hairpin-like structure is known as a precursor of“hsa-miR-6765-5p”.

The term “hsa-miR-6732-5p gene” or “hsa-miR-6732-5p” used hereinincludes the hsa-miR-6732-5p gene (miRBase Accession No. MIMAT0027365)shown in SEQ ID NO: 34, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6732” (miRBase Accession No. MI0022577, SEQ ID NO: 284)having a hairpin-like structure is known as a precursor of“hsa-miR-6732-5p”.

The term “hsa-miR-6787-5p gene” or “hsa-miR-6787-5p” used hereinincludes the hsa-miR-6787-5p gene (miRBase Accession No. MIMAT0027474)shown in SEQ ID NO: 35, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6787” (miRBase Accession No. MI0022632, SEQ ID NO: 285)having a hairpin-like structure is known as a precursor of“hsa-miR-6787-5p”.

The term “hsa-miR-6737-5p gene” or “hsa-miR-6737-5p” used hereinincludes the hsa-miR-6737-5p gene (miRBase Accession No. MIMAT0027375)shown in SEQ ID NO: 36, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6737” (miRBase Accession No. MI0022582, SEQ ID NO: 286)having a hairpin-like structure is known as a precursor of“hsa-miR-6737-5p”.

The term “hsa-miR-128-2-5p gene” or “hsa-miR-128-2-5p” used hereinincludes the hsa-miR-128-2-5p gene (miRBase Accession No. MIMAT0031095)shown in SEQ ID NO: 37, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p.735-739. Also, “hsa-mir-128-2” (miRBase Accession No. MI0000727, SEQ IDNO: 287) having a hairpin-like structure is known as a precursor of“hsa-miR-128-2-5p”.

The term “hsa-miR-4270 gene” or “hsa-miR-4270” used herein includes thehsa-miR-4270 gene (miRBase Accession No. MIMAT0016900) shown in SEQ IDNO: 38, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4270”(miRBase Accession No. MI0015878, SEQ ID NO: 288) having a hairpin-likestructure is known as a precursor of “hsa-miR-4270”.

The term “hsa-miR-6861-5p gene” or “hsa-miR-6861-5p” used hereinincludes the hsa-miR-6861-5p gene (miRBase Accession No. MIMAT0027623)shown in SEQ ID NO: 39, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6861” (miRBase Accession No. MI0022708, SEQ ID NO: 289)having a hairpin-like structure is known as a precursor of“hsa-miR-6861-5p”.

The term “hsa-miR-6756-5p gene” or “hsa-miR-6756-5p” used hereinincludes the hsa-miR-6756-5p gene (miRBase Accession No. MIMAT0027412)shown in SEQ ID NO: 40, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6756” (miRBase Accession No. MI0022601, SEQ ID NO: 290)having a hairpin-like structure is known as a precursor of“hsa-miR-6756-5p”.

The term “hsa-miR-1229-5p gene” or “hsa-miR-1229-5p” used hereinincludes the hsa-miR-1229-5p gene (miRBase Accession No. MIMAT0022942)shown in SEQ ID NO: 41, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1229” (miRBase Accession No. MI0006319, SEQ ID NO: 291)having a hairpin-like structure is known as a precursor of“hsa-miR-1229-5p”.

The term “hsa-miR-6891-5p gene” or “hsa-miR-6891-5p” used hereinincludes the hsa-miR-6891-5p gene (miRBase Accession No. MIMAT0027682)shown in SEQ ID NO: 42, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6891” (miRBase Accession No. MI0022738, SEQ ID NO: 292)having a hairpin-like structure is known as a precursor of“hsa-miR-6891-5p”.

The term “hsa-miR-6848-5p gene” or “hsa-miR-6848-5p” used hereinincludes the hsa-miR-6848-5p gene (miRBase Accession No. MIMAT0027596)shown in SEQ ID NO: 43, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6848” (miRBase Accession No. MI0022694, SEQ ID NO: 293)having a hairpin-like structure is known as a precursor of“hsa-miR-6848-5p”.

The term “hsa-miR-1237-5p gene” or “hsa-miR-1237-5p” used hereinincludes the hsa-miR-1237-5p gene (miRBase Accession No. MIMAT0022946)shown in SEQ ID NO: 44, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1237” (miRBase Accession No. MI0006327, SEQ ID NO: 294)having a hairpin-like structure is known as a precursor of“hsa-miR-1237-5p”.

The term “hsa-miR-30c-1-3p gene” or “hsa-miR-30c-1-3p” used hereinincludes the hsa-miR-30c-1-3p gene (miRBase Accession No. MIMAT0004674)shown in SEQ ID NO: 45, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p.735-739. Also, “hsa-mir-30c-1” (miRBase Accession No. MI0000736, SEQ IDNO: 295) having a hairpin-like structure is known as a precursor of“hsa-miR-30c-1-3p”.

The term “hsa-miR-1233-5p gene” or “hsa-miR-1233-5p” used hereinincludes the hsa-miR-1233-5p gene (miRBase Accession No. MIMAT0022943)shown in SEQ ID NO: 46, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1233-1 and hsa-mir-1233-2” (miRBase Accession Nos.MI0006323 and MI0015973, SEQ ID NOs: 296 and 297) having a hairpin-likestructure are known as a precursor of “hsa-miR-1233-5p”.

The term “hsa-miR-211-3p gene” or “hsa-miR-211-3p” used herein includesthe hsa-miR-211-3p gene (miRBase Accession No. MIMAT0022694) shown inSEQ ID NO: 47, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLim L P et al., 2003, Science, Vol. 299, p. 1540. Also, “hsa-mir-211”(miRBase Accession No. MI0000287, SEQ ID NO: 298) having a hairpin-likestructure is known as a precursor of “hsa-miR-211-3p”.

The term “hsa-miR-4758-5p gene” or “hsa-miR-4758-5p” used hereinincludes the hsa-miR-4758-5p gene (miRBase Accession No. MIMAT0019903)shown in SEQ ID NO: 48, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4758” (miRBase Accession No. MI0017399, SEQ ID NO: 299)having a hairpin-like structure is known as a precursor of“hsa-miR-4758-5p”.

The term “hsa-miR-614 gene” or “hsa-miR-614” used herein includes thehsa-miR-614 gene (miRBase Accession No. MIMAT0003282) shown in SEQ IDNO: 49, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, VOL. 103, p.3687-3692. Also, “hsa-mir-614” (miRBase Accession No. MI0003627, SEQ IDNO: 300) having a hairpin-like structure is known as a precursor of“hsa-miR-614”.

The term “hsa-miR-6746-5p gene” or “hsa-miR-6746-5p” used hereinincludes the hsa-miR-6746-5p gene (miRBase Accession No. MIMAT0027392)shown in SEQ ID NO: 50, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6746” (miRBase Accession No. MI0022591, SEQ ID NO: 301)having a hairpin-like structure is known as a precursor of“hsa-miR-6746-5p”.

The term “hsa-miR-1915-5p gene” or “hsa-miR-1915-5p” used hereinincludes the hsa-miR-1915-5p gene (miRBase Accession No. MIMAT0007891)shown in SEQ ID NO: 51, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505.Also, “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 302)having a hairpin-like structure is known as a precursor of“hsa-miR-1915-5p”.

The term “hsa-miR-4688 gene” or “hsa-miR-4688” used herein includes thehsa-miR-4688 gene (miRBase Accession No. MIMAT0019777) shown in SEQ IDNO: 52, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4688” (miRBase Accession No. MI0017321, SEQ ID NO: 303) havinga hairpin-like structure is known as a precursor of “hsa-miR-4688”.

The term “hsa-miR-3917 gene” or “hsa-miR-3917” used herein includes thehsa-miR-3917 gene (miRBase Accession No. MIMAT0018191) shown in SEQ IDNO: 53, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCreighton C J et al., 2010, PLoS One, Vol. 5, e9637. Also,“hsa-mir-3917” (miRBase Accession No. MI0016423, SEQ ID NO: 304) havinga hairpin-like structure is known as a precursor of “hsa-miR-3917”.

The term “hsa-miR-5787 gene” or “hsa-miR-5787” used herein includes thehsa-miR-5787 gene (miRBase Accession No. MIMAT0023252) shown in SEQ IDNO: 54, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inYoo H et al., 2011, Biochem Biophys Res Commun, Vol. 415, p. 567-572.Also, “hsa-mir-5787” (miRBase Accession No. MI0019797, SEQ ID NO: 305)having a hairpin-like structure is known as a precursor of“hsa-miR-5787”.

The term “hsa-miR-4632-5p gene” or “hsa-miR-4632-5p” used hereinincludes the hsa-miR-4632-5p gene (miRBase Accession No. MIMAT0022977)shown in SEQ ID NO: 55, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4632” (miRBase Accession No. MI0017259, SEQ ID NO: 306)having a hairpin-like structure is known as a precursor of“hsa-miR-4632-5p”.

The term “hsa-miR-6126 gene” or “hsa-miR-6126” used herein includes thehsa-miR-6126 gene (miRBase Accession No. MIMAT0024599) shown in SEQ IDNO: 56, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inSmith J L et al., 2012, J Virol, Vol. 86, p. 5278-5287. Also,“hsa-mir-6126” (miRBase Accession No. MI0021260, SEQ ID NO: 307) havinga hairpin-like structure is known as a precursor of “hsa-miR-6126”.

The term “hsa-miR-135a-3p gene” or “hsa-miR-135a-3p” used hereinincludes the hsa-miR-135a-3p gene (miRBase Accession No. MIMAT0004595)shown in SEQ ID NO: 57, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p.735-739. Also, “hsa-mir-135a-1” (miRBase Accession No. MI0000452, SEQ IDNO: 308) having a hairpin-like structure is known as a precursor of“hsa-miR-135a-3p”.

The term “hsa-miR-8063 gene” or “hsa-miR-8063” used herein includes thehsa-miR-8063 gene (miRBase Accession No. MIMAT0030990) shown in SEQ IDNO: 58, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inWang H J et al., 2013, Shock, Vol. 39, p. 480-487. Also, “hsa-mir-8063”(miRBase Accession No. MI0025899, SEQ ID NO: 309) having a hairpin-likestructure is known as a precursor of “hsa-miR-8063”.

The term “hsa-miR-5698 gene” or “hsa-miR-5698” used herein includes thehsa-miR-5698 gene (miRBase Accession No. MIMAT0022491) shown in SEQ IDNO: 59, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inWatahiki A et al., 2011, PLoS One, Vol. 6, e24950. Also, “hsa-mir-5698”(miRBase Accession No. MI0019305, SEQ ID NO: 310) having a hairpin-likestructure is known as a precursor of “hsa-miR-5698”.

The term “hsa-miR-6089 gene” or “hsa-miR-6089” used herein includes thehsa-miR-6089 gene (miRBase Accession No. MIMAT0023714) shown in SEQ IDNO: 60, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inYoo J K et al., 2012, Stem Cells Dev, Vol. 21, p. 2049-2057. Also,“hsa-mir-6089-1 and hsa-mir-6089-2” (miRBase Accession Nos. MI0020366and MI0023563, SEQ ID NOs: 311 and 312) having a hairpin-like structureare known as a precursor of “hsa-miR-6089”.

The term “hsa-miR-498 gene” or “hsa-miR-498” used herein includes thehsa-miR-498 gene (miRBase Accession No. MIMAT0002824) shown in SEQ IDNO: 61, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inBentwich I et al., 2005, Nat Genet, Vol. 37, p. 766-770. Also,“hsa-mir-498” (miRBase Accession No. MI0003142, SEQ ID NO: 313) having ahairpin-like structure is known as a precursor of “hsa-miR-498”.

The term “hsa-miR-296-3p gene” or “hsa-miR-296-3p” used herein includesthe hsa-miR-296-3p gene (miRBase Accession No. MIMAT0004679) shown inSEQ ID NO: 62, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inHoubaviy H B et al., 2003, Dev Cell, Vol. 5, p. 351-358. Also,“hsa-mir-296” (miRBase Accession No. MI0000747, SEQ ID NO: 314) having ahairpin-like structure is known as a precursor of “hsa-miR-296-3p”.

The term “hsa-miR-4419b gene” or “hsa-miR-4419b” used herein includesthe hsa-miR-4419b gene (miRBase Accession No. MIMAT0019034) shown in SEQID NO: 63, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4419b”(miRBase Accession No. MI0016861, SEQ ID NO: 315) having a hairpin-likestructure is known as a precursor of “hsa-miR-4419b”.

The term “hsa-miR-6802-5p gene” or “hsa-miR-6802-5p” used hereinincludes the hsa-miR-6802-5p gene (miRBase Accession No. MIMAT0027504)shown in SEQ ID NO: 64, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6802” (miRBase Accession No. MI0022647, SEQ ID NO: 316)having a hairpin-like structure is known as a precursor of“hsa-miR-6802-5p”.

The term “hsa-miR-6829-5p gene” or “hsa-miR-6829-5p” used hereinincludes the hsa-miR-6829-5p gene (miRBase Accession No. MIMAT0027558)shown in SEQ ID NO: 65, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6829” (miRBase Accession No. MI0022674, SEQ ID NO: 317)having a hairpin-like structure is known as a precursor of“hsa-miR-6829-5p”.

The term “hsa-miR-6803-5p gene” or “hsa-miR-6803-5p” used hereinincludes the hsa-miR-6803-5p gene (miRBase Accession No. MIMAT0027506)shown in SEQ ID NO: 66, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6803” (miRBase Accession No. MI0022648, SEQ ID NO: 318)having a hairpin-like structure is known as a precursor of“hsa-miR-6803-5p”.

The term “hsa-miR-1199-5p gene” or “hsa-miR-1199-5p” used hereinincludes the hsa-miR-1199-5p gene (miRBase Accession No. MIMAT0031119)shown in SEQ ID NO: 67, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Salvi A et al., 2013, Int J Oncol, Vol. 42, p. 391-402.Also, “hsa-mir-1199” (miRBase Accession No. MI0020340, SEQ ID NO: 319)having a hairpin-like structure is known as a precursor of“hsa-miR-1199-5p”.

The term “hsa-miR-6840-3p gene” or “hsa-miR-6840-3p” used hereinincludes the hsa-miR-6840-3p gene (miRBase Accession No. MIMAT0027583)shown in SEQ ID NO: 68, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6840” (miRBase Accession No. MI0022686, SEQ ID NO: 320)having a hairpin-like structure is known as a precursor of“hsa-miR-6840-3p”.

The term “hsa-miR-6752-5p gene” or “hsa-miR-6752-5p” used hereinincludes the hsa-miR-6752-5p gene (miRBase Accession No. MIMAT0027404)shown in SEQ ID NO: 69, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6752” (miRBase Accession No. MI0022597, SEQ ID NO: 321)having a hairpin-like structure is known as a precursor of“hsa-miR-6752-5p”.

The term “hsa-miR-6798-5p gene” or “hsa-miR-6798-5p” used hereinincludes the hsa-miR-6798-5p gene (miRBase Accession No. MIMAT0027496)shown in SEQ ID NO: 70, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6798” (miRBase Accession No. MI0022643, SEQ ID NO: 322)having a hairpin-like structure is known as a precursor of“hsa-miR-6798-5p”.

The term “hsa-miR-6131 gene” or “hsa-miR-6131” used herein includes thehsa-miR-6131 gene (miRBase Accession No. MIMAT0024615) shown in SEQ IDNO: 71, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inDannemann M et al., 2012, Genome Biol Evol, Vol. 4, p. 552-564. Also,“hsa-mir-6131” (miRBase Accession No. MI0021276, SEQ ID NO: 323) havinga hairpin-like structure is known as a precursor of “hsa-miR-6131”.

The term “hsa-miR-4667-5p gene” or “hsa-miR-4667-5p” used hereinincludes the hsa-miR-4667-5p gene (miRBase Accession No. MIMAT0019743)shown in SEQ ID NO: 72, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4667” (miRBase Accession No. MI0017297, SEQ ID NO: 324)having a hairpin-like structure is known as a precursor of“hsa-miR-4667-5p”.

The term “hsa-miR-6510-5p gene” or “hsa-miR-6510-5p” used hereinincludes the hsa-miR-6510-5p gene (miRBase Accession No. MIMAT0025476)shown in SEQ ID NO: 73, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Joyce C E et al., 2011, Hum Mol Genet, Vol. 20, p.4025-4040. Also, “hsa-mir-6510” (miRBase Accession No. MI0022222, SEQ IDNO: 325) having a hairpin-like structure is known as a precursor of“hsa-miR-6510-5p”.

The term “hsa-miR-4690-5p gene” or “hsa-miR-4690-5p” used hereinincludes the hsa-miR-4690-5p gene (miRBase Accession No. MIMAT0019779)shown in SEQ ID NO: 74, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4690” (miRBase Accession No. MI0017323, SEQ ID NO: 326)having a hairpin-like structure is known as a precursor of“hsa-miR-4690-5p”.

The term “hsa-miR-920 gene” or “hsa-miR-920” used herein includes thehsa-miR-920 gene (miRBase Accession No. MIMAT0004970) shown in SEQ IDNO: 75, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inNovotny G W et al., 2007, Int J Androl, Vol. 30, p. 316-326. Also,“hsa-mir-920” (miRBase Accession No. MI0005712, SEQ ID NO: 327) having ahairpin-like structure is known as a precursor of “hsa-miR-920”.

The term “hsa-miR-23b-3p gene” or “hsa-miR-23b-3p” used herein includesthe hsa-miR-23b-3p gene (miRBase Accession No. MIMAT0000418) shown inSEQ ID NO: 76, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also,“hsa-mir-23b” (miRBase Accession No. MI0000439, SEQ ID NO: 328) having ahairpin-like structure is known as a precursor of “hsa-miR-23b-3p”.

The term “hsa-miR-4448 gene” or “hsa-miR-4448” used herein includes thehsa-miR-4448 gene (miRBase Accession No. MIMAT0018967) shown in SEQ IDNO: 77, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4448”(miRBase Accession No. MI0016791, SEQ ID NO: 329) having a hairpin-likestructure is known as a precursor of “hsa-miR-4448”.

The term “hsa-miR-2110 gene” or “hsa-miR-2110” used herein includes thehsa-miR-2110 gene (miRBase Accession No. MIMAT0010133) shown in SEQ IDNO: 78, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inZhu J Y et al., 2009, J Virol, Vol. 83, p. 3333-3341. Also,“hsa-mir-2110” (miRBase Accession No. MI0010629, SEQ ID NO: 330) havinga hairpin-like structure is known as a precursor of “hsa-miR-2110”.

The term “hsa-miR-4706 gene” or “hsa-miR-4706” used herein includes thehsa-miR-4706 gene (miRBase Accession No. MIMAT0019806) shown in SEQ IDNO: 79, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4706” (miRBase Accession No. MI0017339, SEQ ID NO: 331) havinga hairpin-like structure is known as a precursor of “hsa-miR-4706”.

The term “hsa-miR-7845-5p gene” or “hsa-miR-7845-5p” used hereinincludes the hsa-miR-7845-5p gene (miRBase Accession No. MIMAT0030420)shown in SEQ ID NO: 80, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also,“hsa-mir-7845” (miRBase Accession No. MI0025515, SEQ ID NO: 332) havinga hairpin-like structure is known as a precursor of “hsa-miR-7845-5p”.

The term “hsa-miR-6808-5p gene” or “hsa-miR-6808-5p” used hereinincludes the hsa-miR-6808-5p gene (miRBase Accession No. MIMAT0027516)shown in SEQ ID NO: 81, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6808” (miRBase Accession No. MI0022653, SEQ ID NO: 333)having a hairpin-like structure is known as a precursor of“hsa-miR-6808-5p”.

The term “hsa-miR-4447 gene” or “hsa-miR-4447” used herein includes thehsa-miR-4447 gene (miRBase Accession No. MIMAT0018966) shown in SEQ IDNO: 82, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4447”(miRBase Accession No. MI0016790, SEQ ID NO: 334) having a hairpin-likestructure is known as a precursor of “hsa-miR-4447”.

The term “hsa-miR-6869-5p gene” or “hsa-miR-6869-5p” used hereinincludes the hsa-miR-6869-5p gene (miRBase Accession No. MIMAT0027638)shown in SEQ ID NO: 83, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6869” (miRBase Accession No. MI0022716, SEQ ID NO: 335)having a hairpin-like structure is known as a precursor of“hsa-miR-6869-5p”.

The term “hsa-miR-1908-5p gene” or “hsa-miR-1908-5p” used hereinincludes the hsa-miR-1908-5p gene (miRBase Accession No. MIMAT0007881)shown in SEQ ID NO: 84, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505.Also, “hsa-mir-1908” (miRBase Accession No. MI0008329, SEQ ID NO: 336)having a hairpin-like structure is known as a precursor of“hsa-miR-1908-5p”.

The term “hsa-miR-6729-5p gene” or “hsa-miR-6729-5p” used hereinincludes the hsa-miR-6729-5p gene (miRBase Accession No. MIMAT0027359)shown in SEQ ID NO: 85, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6729” (miRBase Accession No. MI0022574, SEQ ID NO: 337)having a hairpin-like structure is known as a precursor of“hsa-miR-6729-5p”.

The term “hsa-miR-5195-3p gene” or “hsa-miR-5195-3p” used hereinincludes the hsa-miR-5195-3p gene (miRBase Accession No. MIMAT0021127)shown in SEQ ID NO: 86, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Schotte D et al., 2011, Leukemia, Vol. 25, p. 1389-1399.Also, “hsa-mir-5195” (miRBase Accession No. MI0018174, SEQ ID NO: 338)having a hairpin-like structure is known as a precursor of“hsa-miR-5195-3p”.

The term “hsa-miR-638 gene” or “hsa-miR-638” used herein includes thehsa-miR-638 gene (miRBase Accession No. MIMAT0003308) shown in SEQ IDNO: 87, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-638” (miRBase Accession No. MI0003653, SEQ IDNO: 339) having a hairpin-like structure is known as a precursor of“hsa-miR-638”.

The term “hsa-miR-6125 gene” or “hsa-miR-6125” used herein includes thehsa-miR-6125 gene (miRBase Accession No. MIMAT0024598) shown in SEQ IDNO: 88, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inSmith J L et al., 2012, J Virol, Vol. 86, p. 5278-5287. Also,“hsa-mir-6125” (miRBase Accession No. MI0021259, SEQ ID NO: 340) havinga hairpin-like structure is known as a precursor of “hsa-miR-6125”.

The term “hsa-miR-3178 gene” or “hsa-miR-3178” used herein includes thehsa-miR-3178 gene (miRBase Accession No. MIMAT0015055) shown in SEQ IDNO: 89, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3178”(miRBase Accession No. MI0014212, SEQ ID NO: 341) having a hairpin-likestructure is known as a precursor of “hsa-miR-3178”.

The term “hsa-miR-3196 gene” or “hsa-miR-3196” used herein includes thehsa-miR-3196 gene (miRBase Accession No. MIMAT0015080) shown in SEQ IDNO: 90, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3196”(miRBase Accession No. MI0014241, SEQ ID NO: 342) having a hairpin-likestructure is known as a precursor of “hsa-miR-3196”.

The term “hsa-miR-8069 gene” or “hsa-miR-8069” used herein includes thehsa-miR-8069 gene (miRBase Accession No. MIMAT0030996) shown in SEQ IDNO: 91, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inWang H J et al., 2013, Shock, Vol. 39, p. 480-487. Also, “hsa-mir-8069-1and hsa-mir-8069-2” (miRBase Accession Nos. MI0025905 and MI0031519, SEQID NOs: 343 and 344) having a hairpin-like structure are known as aprecursor of “hsa-miR-8069”.

The term “hsa-miR-4723-5p gene” or “hsa-miR-4723-5p” used hereinincludes the hsa-miR-4723-5p gene (miRBase Accession No. MIMAT0019838)shown in SEQ ID NO: 92, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4723” (miRBase Accession No. MI0017359, SEQ ID NO: 345)having a hairpin-like structure is known as a precursor of“hsa-miR-4723-5p”.

The term “hsa-miR-4746-3p gene” or “hsa-miR-4746-3p” used hereinincludes the hsa-miR-4746-3p gene (miRBase Accession No. MIMAT0019881)shown in SEQ ID NO: 93, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4746” (miRBase Accession No. MI0017385, SEQ ID NO: 346)having a hairpin-like structure is known as a precursor of“hsa-miR-4746-3p”.

The term “hsa-miR-4689 gene” or “hsa-miR-4689” used herein includes thehsa-miR-4689 gene (miRBase Accession No. MIMAT0019778) shown in SEQ IDNO: 94, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4689” (miRBase Accession No. MI0017322, SEQ ID NO: 347) havinga hairpin-like structure is known as a precursor of “hsa-miR-4689”.

The term “hsa-miR-6816-5p gene” or “hsa-miR-6816-5p” used hereinincludes the hsa-miR-6816-5p gene (miRBase Accession No. MIMAT0027532)shown in SEQ ID NO: 95, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6816” (miRBase Accession No. MI0022661, SEQ ID NO: 348)having a hairpin-like structure is known as a precursor of“hsa-miR-6816-5p”.

The term “hsa-miR-6757-5p gene” or “hsa-miR-6757-5p” used hereinincludes the hsa-miR-6757-5p gene (miRBase Accession No. MIMAT0027414)shown in SEQ ID NO: 96, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6757” (miRBase Accession No. MI0022602, SEQ ID NO: 349)having a hairpin-like structure is known as a precursor of“hsa-miR-6757-5p”.

The term “hsa-miR-7109-5p gene” or “hsa-miR-7109-5p” used hereinincludes the hsa-miR-7109-5p gene (miRBase Accession No. MIMAT0028115)shown in SEQ ID NO: 97, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-7109” (miRBase Accession No. MI0022960, SEQ ID NO: 350)having a hairpin-like structure is known as a precursor of“hsa-miR-7109-5p”.

The term “hsa-miR-6724-5p gene” or “hsa-miR-6724-5p” used hereinincludes the hsa-miR-6724-5p gene (miRBase Accession No. MIMAT0025856)shown in SEQ ID NO: 98, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also,“hsa-mir-6724-1, hsa-mir-6724-2, hsa-mir-6724-3 and hsa-mir-6724-4”(miRBase Accession Nos. MI0022559, MI0031516, MI0031517 and MI0031518,SEQ ID NOs: 351, 352, 353 and 354) having a hairpin-like structure areknown as a precursor of “hsa-miR-6724-5p”.

The term “hsa-miR-1225-3p gene” or “hsa-miR-1225-3p” used hereinincludes the hsa-miR-1225-3p gene (miRBase Accession No. MIMAT0005573)shown in SEQ ID NO: 99, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1225” (miRBase Accession No. MI0006311, SEQ ID NO: 355)having a hairpin-like structure is known as a precursor of“hsa-miR-1225-3p”.

The term “hsa-miR-6875-5p gene” or “hsa-miR-6875-5p” used hereinincludes the hsa-miR-6875-5p gene (miRBase Accession No. MIMAT0027650)shown in SEQ ID NO: 100, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6875” (miRBase Accession No. MI0022722, SEQ ID NO: 356)having a hairpin-like structure is known as a precursor of“hsa-miR-6875-5p”.

The term “hsa-miR-7108-5p gene” or “hsa-miR-7108-5p” used hereinincludes the hsa-miR-7108-5p gene (miRBase Accession No. MIMAT0028113)shown in SEQ ID NO: 101, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-7108” (miRBase Accession No. MI0022959, SEQ ID NO: 357)having a hairpin-like structure is known as a precursor of“hsa-miR-7108-5p”.

The term “hsa-miR-4508 gene” or “hsa-miR-4508” used herein includes thehsa-miR-4508 gene (miRBase Accession No. MIMAT0019045) shown in SEQ IDNO: 102, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4508”(miRBase Accession No. MI0016872, SEQ ID NO: 358) having a hairpin-likestructure is known as a precursor of “hsa-miR-4508”.

The term “hsa-miR-6085 gene” or “hsa-miR-6085” used herein includes thehsa-miR-6085 gene (miRBase Accession No. MIMAT0023710) shown in SEQ IDNO: 103, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inVoellenkle C et al., 2012, RNA, Vol. 18, p. 472-484. Also,“hsa-mir-6085” (miRBase Accession No. MI0020362, SEQ ID NO: 359) havinga hairpin-like structure is known as a precursor of “hsa-miR-6085”.

The term “hsa-miR-6779-5p gene” or “hsa-miR-6779-5p” used hereinincludes the hsa-miR-6779-5p gene (miRBase Accession No. MIMAT0027458)shown in SEQ ID NO: 104, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6779” (miRBase Accession No. MI0022624, SEQ ID NO: 360)having a hairpin-like structure is known as a precursor of“hsa-miR-6779-5p”.

The term “hsa-miR-642a-3p gene” or “hsa-miR-642a-3p” used hereinincludes the hsa-miR-642a-3p gene (miRBase Accession No. MIMAT0020924)shown in SEQ ID NO: 105, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Cummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103,p. 3687-3692. Also, “hsa-mir-642a” (miRBase Accession No. MI0003657, SEQID NO: 361) having a hairpin-like structure is known as a precursor of“hsa-miR-642a-3p”.

The term “hsa-miR-4695-5p gene” or “hsa-miR-4695-5p” used hereinincludes the hsa-miR-4695-5p gene (miRBase Accession No. MIMAT0019788)shown in SEQ ID NO: 106, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4695” (miRBase Accession No. MI0017328, SEQ ID NO: 362)having a hairpin-like structure is known as a precursor of“hsa-miR-4695-5p”.

The term “hsa-miR-7847-3p gene” or “hsa-miR-7847-3p” used hereinincludes the hsa-miR-7847-3p gene (miRBase Accession No. MIMAT0030422)shown in SEQ ID NO: 107, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also,“hsa-mir-7847” (miRBase Accession No. MI0025517, SEQ ID NO: 363) havinga hairpin-like structure is known as a precursor of “hsa-miR-7847-3p”.

The term “hsa-miR-3197 gene” or “hsa-miR-3197” used herein includes thehsa-miR-3197 gene (miRBase Accession No. MIMAT0015082) shown in SEQ IDNO: 108, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3197”(miRBase Accession No. MI0014245, SEQ ID NO: 364) having a hairpin-likestructure is known as a precursor of “hsa-miR-3197”.

The term “hsa-miR-6769b-5p gene” or “hsa-miR-6769b-5p” used hereinincludes the hsa-miR-6769b-5p gene (miRBase Accession No. MIMAT0027620)shown in SEQ ID NO: 109, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6769b” (miRBase Accession No. MI0022706, SEQ ID NO: 365)having a hairpin-like structure is known as a precursor of“hsa-miR-6769b-5p”.

The term “hsa-miR-7641 gene” or “hsa-miR-7641” used herein includes thehsa-miR-7641 gene (miRBase Accession No. MIMAT0029782) shown in SEQ IDNO: 110, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inYoo J K et al., 2013, Arch Pharm Res, Vol. 36, p. 353-358. Also,“hsa-mir-7641-1 and hsa-mir-7641-2” (miRBase Accession Nos. MI0024975and MI0024976, SEQ ID NOs: 366 and 367) having a hairpin-like structureare known as a precursor of “hsa-miR-7641”.

The term “hsa-miR-187-5p gene” or “hsa-miR-187-5p” used herein includesthe hsa-miR-187-5p gene (miRBase Accession No. MIMAT0004561) shown inSEQ ID NO: 111, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLim L P et al., 2003, Science, Vol. 299, p. 1540. Also, “hsa-mir-187”(miRBase Accession No. MI0000274, SEQ ID NO: 368) having a hairpin-likestructure is known as a precursor of “hsa-miR-187-5p”.

The term “hsa-miR-3185 gene” or “hsa-miR-3185” used herein includes thehsa-miR-3185 gene (miRBase Accession No. MIMAT0015065) shown in SEQ IDNO: 112, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3185”(miRBase Accession No. MI0014227, SEQ ID NO: 369) having a hairpin-likestructure is known as a precursor of “hsa-miR-3185”.

The term “hsa-miR-2861 gene” or “hsa-miR-2861” used herein includes thehsa-miR-2861 gene (miRBase Accession No. MIMAT0013802) shown in SEQ IDNO: 113, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLi H et al., 2009, J Clin Invest, Vol. 119, p. 3666-3677. Also,“hsa-mir-2861” (miRBase Accession No. MI0013006, SEQ ID NO: 370) havinga hairpin-like structure is known as a precursor of “hsa-miR-2861”.

The term “hsa-miR-3940-5p gene” or “hsa-miR-3940-5p” used hereinincludes the hsa-miR-3940-5p gene (miRBase Accession No. MIMAT0019229)shown in SEQ ID NO: 114, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Liao J Y et al., 2010, PLoS One, Vol. 5, e10563. Also,“hsa-mir-3940” (miRBase Accession No. MI0016597, SEQ ID NO: 371) havinga hairpin-like structure is known as a precursor of “hsa-miR-3940-5p”.

The term “hsa-miR-1203 gene” or “hsa-miR-1203” used herein includes thehsa-miR-1203 gene (miRBase Accession No. MIMAT0005866) shown in SEQ IDNO: 115, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inMarton S et al., 2008, Leukemia, Vol. 22, p. 330-338. Also,“hsa-mir-1203” (miRBase Accession No. MI0006335, SEQ ID NO: 372) havinga hairpin-like structure is known as a precursor of “hsa-miR-1203”.

The term “hsa-miR-615-5p gene” or “hsa-miR-615-5p” used herein includesthe hsa-miR-615-5p gene (miRBase Accession No. MIMAT0004804) shown inSEQ ID NO: 116, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-615” (miRBase Accession No. MI0003628, SEQ IDNO: 373) having a hairpin-like structure is known as a precursor of“hsa-miR-615-5p”.

The term “hsa-miR-4787-5p gene” or “hsa-miR-4787-5p” used hereinincludes the hsa-miR-4787-5p gene (miRBase Accession No. MIMAT0019956)shown in SEQ ID NO: 117, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4787” (miRBase Accession No. MI0017434, SEQ ID NO: 374)having a hairpin-like structure is known as a precursor of“hsa-miR-4787-5p”.

The term “hsa-miR-1343-3p gene” or “hsa-miR-1343-3p” used hereinincludes the hsa-miR-1343-3p gene (miRBase Accession No. MIMAT0019776)shown in SEQ ID NO: 118, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-1343” (miRBase Accession No. MI0017320, SEQ ID NO: 375)having a hairpin-like structure is known as a precursor of“hsa-miR-1343-3p”.

The term “hsa-miR-6813-5p gene” or “hsa-miR-6813-5p” used hereinincludes the hsa-miR-6813-5p gene (miRBase Accession No. MIMAT0027526)shown in SEQ ID NO: 119, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6813” (miRBase Accession No. MI0022658, SEQ ID NO: 376)having a hairpin-like structure is known as a precursor of“hsa-miR-6813-5p”.

The term “hsa-miR-1225-5p gene” or “hsa-miR-1225-5p” used hereinincludes the hsa-miR-1225-5p gene (miRBase Accession No. MIMAT0005572)shown in SEQ ID NO: 120, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1225” (miRBase Accession No. MI0006311, SEQ ID NO: 377)having a hairpin-like structure is known as a precursor of“hsa-miR-1225-5p”.

The term “hsa-miR-602 gene” or “hsa-miR-602” used herein includes thehsa-miR-602 gene (miRBase Accession No. MIMAT0003270) shown in SEQ IDNO: 121, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-602” (miRBase Accession No. MI0003615, SEQ IDNO: 378) having a hairpin-like structure is known as a precursor of“hsa-miR-602”.

The term “hsa-miR-4488 gene” or “hsa-miR-4488” used herein includes thehsa-miR-4488 gene (miRBase Accession No. MIMAT0019022) shown in SEQ IDNO: 122, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4488”(miRBase Accession No. MI0016849, SEQ ID NO: 379) having a hairpin-likestructure is known as a precursor of “hsa-miR-4488”.

The term “hsa-miR-125a-3p gene” or “hsa-miR-125a-3p” used hereinincludes the hsa-miR-125a-3p gene (miRBase Accession No. MIMAT0004602)shown in SEQ ID NO: 123, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p.735-739. Also, “hsa-mir-125a” (miRBase Accession No. MI0000469, SEQ IDNO: 380) having a hairpin-like structure is known as a precursor of“hsa-miR-125a-3p”.

The term “hsa-miR-5100 gene” or “hsa-miR-5100” used herein includes thehsa-miR-5100 gene (miRBase Accession No. MIMAT0022259) shown in SEQ IDNO: 124, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inTandon M et al., 2012, Oral Dis, Vol. 18, p. 127-131. Also,“hsa-mir-5100” (miRBase Accession No. MI0019116, SEQ ID NO: 381) havinga hairpin-like structure is known as a precursor of “hsa-miR-5100”.

The term “hsa-miR-4294 gene” or “hsa-miR-4294” used herein includes thehsa-miR-4294 gene (miRBase Accession No. MIMAT0016849) shown in SEQ IDNO: 125, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4294”(miRBase Accession No. MI0015827, SEQ ID NO: 382) having a hairpin-likestructure is known as a precursor of “hsa-miR-4294”.

The term “hsa-miR-1231 gene” or “hsa-miR-1231” used herein includes thehsa-miR-1231 gene (miRBase Accession No. MIMAT0005586) shown in SEQ IDNO: 126, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inBerezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336. Also,“hsa-mir-1231” (miRBase Accession No. MI0006321, SEQ ID NO: 383) havinga hairpin-like structure is known as a precursor of “hsa-miR-1231”.

The term “hsa-miR-6765-3p gene” or “hsa-miR-6765-3p” used hereinincludes the hsa-miR-6765-3p gene (miRBase Accession No. MIMAT0027431)shown in SEQ ID NO: 127, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6765” (miRBase Accession No. MI0022610, SEQ ID NO: 384)having a hairpin-like structure is known as a precursor of“hsa-miR-6765-3p”.

The term “hsa-miR-4442 gene” or “hsa-miR-4442” used herein includes thehsa-miR-4442 gene (miRBase Accession No. MIMAT0018960) shown in SEQ IDNO: 128, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4442”(miRBase Accession No. MI0016785, SEQ ID NO: 385) having a hairpin-likestructure is known as a precursor of “hsa-miR-4442”.

The term “hsa-miR-718 gene” or “hsa-miR-718” used herein includes thehsa-miR-718 gene (miRBase Accession No. MIMAT0012735) shown in SEQ IDNO: 129, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inArtzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. Also,“hsa-mir-718” (miRBase Accession No. MI0012489, SEQ ID NO: 386) having ahairpin-like structure is known as a precursor of “hsa-miR-718”.

The term “hsa-miR-6780b-5p gene” or “hsa-miR-6780b-5p” used hereinincludes the hsa-miR-6780b-5p gene (miRBase Accession No. MIMAT0027572)shown in SEQ ID NO: 130, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6780b” (miRBase Accession No. MI0022681, SEQ ID NO: 387)having a hairpin-like structure is known as a precursor of“hsa-miR-6780b-5p”.

The term “hsa-miR-6090 gene” or “hsa-miR-6090” used herein includes thehsa-miR-6090 gene (miRBase Accession No. MIMAT0023715) shown in SEQ IDNO: 131, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inYoo J K et al., 2012, Stem Cells Dev, Vol. 21, p. 2049-2057. Also,“hsa-mir-6090” (miRBase Accession No. MI0020367, SEQ ID NO: 388) havinga hairpin-like structure is known as a precursor of “hsa-miR-6090”.

The term “hsa-miR-6845-5p gene” or “hsa-miR-6845-5p” used hereinincludes the hsa-miR-6845-5p gene (miRBase Accession No. MIMAT0027590)shown in SEQ ID NO: 132, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6845” (miRBase Accession No. MI0022691, SEQ ID NO: 389)having a hairpin-like structure is known as a precursor of“hsa-miR-6845-5p”.

The term “hsa-miR-4741 gene” or “hsa-miR-4741” used herein includes thehsa-miR-4741 gene (miRBase Accession No. MIMAT0019871) shown in SEQ IDNO: 133, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4741” (miRBase Accession No. MI0017379, SEQ ID NO: 390) havinga hairpin-like structure is known as a precursor of “hsa-miR-4741”.

The term “hsa-miR-4467 gene” or “hsa-miR-4467” used herein includes thehsa-miR-4467 gene (miRBase Accession No. MIMAT0018994) shown in SEQ IDNO: 134, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4467”(miRBase Accession No. MI0016818, SEQ ID NO: 391) having a hairpin-likestructure is known as a precursor of “hsa-miR-4467”.

The term “hsa-miR-4707-5p gene” or “hsa-miR-4707-5p” used hereinincludes the hsa-miR-4707-5p gene (miRBase Accession No. MIMAT0019807)shown in SEQ ID NO: 135, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4707” (miRBase Accession No. MI0017340, SEQ ID NO: 392)having a hairpin-like structure is known as a precursor of“hsa-miR-4707-5p”.

The term “hsa-miR-4271 gene” or “hsa-miR-4271” used herein includes thehsa-miR-4271 gene (miRBase Accession No. MIMAT0016901) shown in SEQ IDNO: 136, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4271”(miRBase Accession No. MI0015879, SEQ ID NO: 393) having a hairpin-likestructure is known as a precursor of “hsa-miR-4271”.

The term “hsa-miR-4673 gene” or “hsa-miR-4673” used herein includes thehsa-miR-4673 gene (miRBase Accession No. MIMAT0019755) shown in SEQ IDNO: 137, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4673” (miRBase Accession No. MI0017304, SEQ ID NO: 394) havinga hairpin-like structure is known as a precursor of “hsa-miR-4673”.

The term “hsa-miR-3184-5p gene” or “hsa-miR-3184-5p” used hereinincludes the hsa-miR-3184-5p gene (miRBase Accession No. MIMAT0015064)shown in SEQ ID NO: 138, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Stark M S et al., 2010, PLoS One, Vol. 5, e9685. Also,“hsa-mir-3184” (miRBase Accession No. MI0014226, SEQ ID NO: 395) havinga hairpin-like structure is known as a precursor of “hsa-miR-3184-5p”.

The term “hsa-miR-1469 gene” or “hsa-miR-1469” used herein includes thehsa-miR-1469 gene (miRBase Accession No. MIMAT0007347) shown in SEQ IDNO: 139, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inKawaji H et al., 2008, BMC Genomics, Vol. 9, p. 157. Also,“hsa-mir-1469” (miRBase Accession No. MI0007074, SEQ ID NO: 396) havinga hairpin-like structure is known as a precursor of “hsa-miR-1469”.

The term “hsa-miR-4640-5p gene” or “hsa-miR-4640-5p” used hereinincludes the hsa-miR-4640-5p gene (miRBase Accession No. MIMAT0019699)shown in SEQ ID NO: 140, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4640” (miRBase Accession No. MI0017267, SEQ ID NO: 397)having a hairpin-like structure is known as a precursor of“hsa-miR-4640-5p”.

The term “hsa-miR-663a gene” or “hsa-miR-663a” used herein includes thehsa-miR-663a gene (miRBase Accession No. MIMAT0003326) shown in SEQ IDNO: 141, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-663a” (miRBase Accession No. MI0003672, SEQ IDNO: 398) having a hairpin-like structure is known as a precursor of“hsa-miR-663a”.

The term “hsa-miR-6791-5p gene” or “hsa-miR-6791-5p” used hereinincludes the hsa-miR-6791-5p gene (miRBase Accession No. MIMAT0027482)shown in SEQ ID NO: 142, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6791” (miRBase Accession No. MI0022636, SEQ ID NO: 399)having a hairpin-like structure is known as a precursor of“hsa-miR-6791-5p”.

The term “hsa-miR-6826-5p gene” or “hsa-miR-6826-5p” used hereinincludes the hsa-miR-6826-5p gene (miRBase Accession No. MIMAT0027552)shown in SEQ ID NO: 143, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6826” (miRBase Accession No. MI0022671, SEQ ID NO: 400)having a hairpin-like structure is known as a precursor of“hsa-miR-6826-5p”.

The term “hsa-miR-4433b-3p gene” or “hsa-miR-4433b-3p” used hereinincludes the hsa-miR-4433b-3p gene (miRBase Accession No. MIMAT0030414)shown in SEQ ID NO: 144, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ple H et al., 2012, PLoS One, Vol. 7, e50746. Also,“hsa-mir-4433b” (miRBase Accession No. MI0025511, SEQ ID NO: 401) havinga hairpin-like structure is known as a precursor of “hsa-miR-4433b-3p”.

The term “hsa-miR-1915-3p gene” or “hsa-miR-1915-3p” used hereinincludes the hsa-miR-1915-3p gene (miRBase Accession No. MIMAT0007892)shown in SEQ ID NO: 145, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Bar M et al., 2008, Stem Cells, Vol. 26, p. 2496-2505.Also, “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 402)having a hairpin-like structure is known as a precursor of“hsa-miR-1915-3p”.

The term “hsa-miR-4417 gene” or “hsa-miR-4417” used herein includes thehsa-miR-4417 gene (miRBase Accession No. MIMAT0018929) shown in SEQ IDNO: 146, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4417”(miRBase Accession No. MI0016753, SEQ ID NO: 403) having a hairpin-likestructure is known as a precursor of “hsa-miR-4417”.

The term “hsa-miR-4449 gene” or “hsa-miR-4449” used herein includes thehsa-miR-4449 gene (miRBase Accession No. MIMAT0018968) shown in SEQ IDNO: 147, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4449”(miRBase Accession No. MI0016792, SEQ ID NO: 404) having a hairpin-likestructure is known as a precursor of “hsa-miR-4449”.

The term “hsa-miR-4707-3p gene” or “hsa-miR-4707-3p” used hereinincludes the hsa-miR-4707-3p gene (miRBase Accession No. MIMAT0019808)shown in SEQ ID NO: 148, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4707” (miRBase Accession No. MI0017340, SEQ ID NO: 405)having a hairpin-like structure is known as a precursor of“hsa-miR-4707-3p”.

The term “hsa-miR-3180-3p gene” or “hsa-miR-3180-3p” used hereinincludes the hsa-miR-3180-3p gene (miRBase Accession No. MIMAT0015058)shown in SEQ ID NO: 149, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Creighton C J et al., 2010, PLoS One, Vol. 5, e9637. Also,“hsa-mir-3180-1, hsa-mir-3180-2 and hsa-mir-3180-3” (miRBase AccessionNos. MI0014214, MI0014215 and MI0014217, SEQ ID NOs: 406, 407 and 408)having a hairpin-like structure are known as a precursor of“hsa-miR-3180-3p”.

The term “hsa-miR-5585-3p gene” or “hsa-miR-5585-3p” used hereinincludes the hsa-miR-5585-3p gene (miRBase Accession No. MIMAT0022286)shown in SEQ ID NO: 150, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Friedlander M R et al., 2012, Nucleic Acids Res, Vol. 40,p. 37-52. Also, “hsa-mir-5585” (miRBase Accession No. MI0019142, SEQ IDNO: 409) having a hairpin-like structure is known as a precursor of“hsa-miR-5585-3p”.

The term “hsa-miR-1268a gene” or “hsa-miR-1268a” used herein includesthe hsa-miR-1268a gene (miRBase Accession No. MIMAT0005922) shown in SEQID NO: 151, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inMorin R D et al., 2008, Genome Res, Vol. 18, p. 610-621. Also,“hsa-mir-1268a” (miRBase Accession No. MI0006405, SEQ ID NO: 410) havinga hairpin-like structure is known as a precursor of “hsa-miR-1268a”.

The term “hsa-miR-8072 gene” or “hsa-miR-8072” used herein includes thehsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) shown in SEQ IDNO: 152, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inWang H J et al., 2013, Shock, Vol. 39, p. 480-487. Also, “hsa-mir-8072”(miRBase Accession No. MI0025908, SEQ ID NO: 411) having a hairpin-likestructure is known as a precursor of “hsa-miR-8072”.

The term “hsa-miR-296-5p gene” or “hsa-miR-296-5p” used herein includesthe hsa-miR-296-5p gene (miRBase Accession No. MIMAT0000690) shown inSEQ ID NO: 153, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inHoubaviy H B et al., 2003, Dev Cell, Vol. 5, p. 351-358. Also,“hsa-mir-296” (miRBase Accession No. MI0000747, SEQ ID NO: 412) having ahairpin-like structure is known as a precursor of “hsa-miR-296-5p”.

The term “hsa-miR-204-3p gene” or “hsa-miR-204-3p” used herein includesthe hsa-miR-204-3p gene (miRBase Accession No. MIMAT0022693) shown inSEQ ID NO: 154, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLim L P et al., 2003, Science, Vol. 299, p. 1540. Also, “hsa-mir-204”(miRBase Accession No. MI0000284, SEQ ID NO: 413) having a hairpin-likestructure is known as a precursor of “hsa-miR-204-3p”.

The term “hsa-miR-4454 gene” or “hsa-miR-4454” used herein includes thehsa-miR-4454 gene (miRBase Accession No. MIMAT0018976) shown in SEQ IDNO: 155, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4454”(miRBase Accession No. MI0016800, SEQ ID NO: 414) having a hairpin-likestructure is known as a precursor of “hsa-miR-4454”.

The term “hsa-miR-6722-3p gene” or “hsa-miR-6722-3p” used hereinincludes the hsa-miR-6722-3p gene (miRBase Accession No. MIMAT0025854)shown in SEQ ID NO: 156, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also,“hsa-mir-6722” (miRBase Accession No. MI0022557, SEQ ID NO: 415) havinga hairpin-like structure is known as a precursor of “hsa-miR-6722-3p”.

The term “hsa-miR-1290 gene” or “hsa-miR-1290” used herein includes thehsa-miR-1290 gene (miRBase Accession No. MIMAT0005880) shown in SEQ IDNO: 157, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inMorin R D et al., 2008, Genome Res, Vol. 18, p. 610-621. Also,“hsa-mir-1290” (miRBase Accession No. MI0006352, SEQ ID NO: 416) havinga hairpin-like structure is known as a precursor of “hsa-miR-1290”.

The term “hsa-miR-3622a-5p gene” or “hsa-miR-3622a-5p” used hereinincludes the hsa-miR-3622a-5p gene (miRBase Accession No. MIMAT0018003)shown in SEQ ID NO: 158, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also,“hsa-mir-3622a” (miRBase Accession No. MI0016013, SEQ ID NO: 417) havinga hairpin-like structure is known as a precursor of “hsa-miR-3622a-5p”.

The term “hsa-miR-939-5p gene” or “hsa-miR-939-5p” used herein includesthe hsa-miR-939-5p gene (miRBase Accession No. MIMAT0004982) shown inSEQ ID NO: 159, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLui W O et al., 2007, Cancer Res, Vol. 67, p. 6031-6043. Also,“hsa-mir-939” (miRBase Accession No. MI0005761, SEQ ID NO: 418) having ahairpin-like structure is known as a precursor of “hsa-miR-939-5p”.

The term “hsa-miR-675-5p gene” or “hsa-miR-675-5p” used herein includesthe hsa-miR-675-5p gene (miRBase Accession No. MIMAT0004284) shown inSEQ ID NO: 160, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCai X et al., 2007, RNA, Vol. 13, p. 313-316. Also, “hsa-mir-675”(miRBase Accession No. MI0005416, SEQ ID NO: 419) having a hairpin-likestructure is known as a precursor of “hsa-miR-675-5p”.

The term “hsa-miR-3131 gene” or “hsa-miR-3131” used herein includes thehsa-miR-3131 gene (miRBase Accession No. MIMAT0014996) shown in SEQ IDNO: 161, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3131”(miRBase Accession No. MI0014151, SEQ ID NO: 420) having a hairpin-likestructure is known as a precursor of “hsa-miR-3131”.

The term “hsa-miR-4648 gene” or “hsa-miR-4648” used herein includes thehsa-miR-4648 gene (miRBase Accession No. MIMAT0019710) shown in SEQ IDNO: 162, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4648” (miRBase Accession No. MI0017275, SEQ ID NO: 421) havinga hairpin-like structure is known as a precursor of “hsa-miR-4648”.

The term “hsa-miR-1268b gene” or “hsa-miR-1268b” used herein includesthe hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) shown in SEQID NO: 163, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-1268b”(miRBase Accession No. MI0016748, SEQ ID NO: 422) having a hairpin-likestructure is known as a precursor of “hsa-miR-1268b”.

The term “hsa-miR-6741-5p gene” or “hsa-miR-6741-5p” used hereinincludes the hsa-miR-6741-5p gene (miRBase Accession No. MIMAT0027383)shown in SEQ ID NO: 164, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6741” (miRBase Accession No. MI0022586, SEQ ID NO: 423)having a hairpin-like structure is known as a precursor of“hsa-miR-6741-5p”.

The term “hsa-miR-6893-5p gene” or “hsa-miR-6893-5p” used hereinincludes the hsa-miR-6893-5p gene (miRBase Accession No. MIMAT0027686)shown in SEQ ID NO: 165, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6893” (miRBase Accession No. MI0022740, SEQ ID NO: 424)having a hairpin-like structure is known as a precursor of“hsa-miR-6893-5p”.

The term “hsa-miR-3162-5p gene” or “hsa-miR-3162-5p” used hereinincludes the hsa-miR-3162-5p gene (miRBase Accession No. MIMAT0015036)shown in SEQ ID NO: 166, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Stark M S et al., 2010, PLoS One, Vol. 5, e9685. Also,“hsa-mir-3162” (miRBase Accession No. MI0014192, SEQ ID NO: 425) havinga hairpin-like structure is known as a precursor of “hsa-miR-3162-5p”.

The term “hsa-miR-642b-3p gene” or “hsa-miR-642b-3p” used hereinincludes the hsa-miR-642b-3p gene (miRBase Accession No. MIMAT0018444)shown in SEQ ID NO: 167, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Witten D et al., 2010, BMC Biol, Vol. 8, p. 58. Also,“hsa-mir-642b” (miRBase Accession No. MI0016685, SEQ ID NO: 426) havinga hairpin-like structure is known as a precursor of “hsa-miR-642b-3p”.

The term “hsa-miR-4734 gene” or “hsa-miR-4734” used herein includes thehsa-miR-4734 gene (miRBase Accession No. MIMAT0019859) shown in SEQ IDNO: 168, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4734” (miRBase Accession No. MI0017371, SEQ ID NO: 427) havinga hairpin-like structure is known as a precursor of “hsa-miR-4734”.

The term “hsa-miR-150-3p gene” or “hsa-miR-150-3p” used herein includesthe hsa-miR-150-3p gene (miRBase Accession No. MIMAT0004610) shown inSEQ ID NO: 169, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p. 735-739. Also,“hsa-mir-150” (miRBase Accession No. MI0000479, SEQ ID NO: 428) having ahairpin-like structure is known as a precursor of “hsa-miR-150-3p”.

The term “hsa-miR-8089 gene” or “hsa-miR-8089” used herein includes thehsa-miR-8089 gene (miRBase Accession No. MIMAT0031016) shown in SEQ IDNO: 170, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inWang H J et al., 2013, Shock, Vol. 39, p. 480-487. Also, “hsa-mir-8089”(miRBase Accession No. MI0025925, SEQ ID NO: 429) having a hairpin-likestructure is known as a precursor of “hsa-miR-8089”.

The term “hsa-miR-6805-3p gene” or “hsa-miR-6805-3p” used hereinincludes the hsa-miR-6805-3p gene (miRBase Accession No. MIMAT0027511)shown in SEQ ID NO: 171, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6805” (miRBase Accession No. MI0022650, SEQ ID NO: 430)having a hairpin-like structure is known as a precursor of“hsa-miR-6805-3p”.

The term “hsa-miR-7113-3p gene” or “hsa-miR-7113-3p” used hereinincludes the hsa-miR-7113-3p gene (miRBase Accession No. MIMAT0028124)shown in SEQ ID NO: 172, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-7113” (miRBase Accession No. MI0022964, SEQ ID NO: 431)having a hairpin-like structure is known as a precursor of“hsa-miR-7113-3p”.

The term “hsa-miR-6850-5p gene” or “hsa-miR-6850-5p” used hereinincludes the hsa-miR-6850-5p gene (miRBase Accession No. MIMAT0027600)shown in SEQ ID NO: 173, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6850” (miRBase Accession No. MI0022696, SEQ ID NO: 432)having a hairpin-like structure is known as a precursor of“hsa-miR-6850-5p”.

The term “hsa-miR-6799-5p gene” or “hsa-miR-6799-5p” used hereinincludes the hsa-miR-6799-5p gene (miRBase Accession No. MIMAT0027498)shown in SEQ ID NO: 174, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6799” (miRBase Accession No. MI0022644, SEQ ID NO: 433)having a hairpin-like structure is known as a precursor of“hsa-miR-6799-5p”.

The term “hsa-miR-6768-5p gene” or “hsa-miR-6768-5p” used hereinincludes the hsa-miR-6768-5p gene (miRBase Accession No. MIMAT0027436)shown in SEQ ID NO: 175, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6768” (miRBase Accession No. MI0022613, SEQ ID NO: 434)having a hairpin-like structure is known as a precursor of“hsa-miR-6768-5p”.

The term “hsa-miR-92b-5p gene” or “hsa-miR-92b-5p” used herein includesthe hsa-miR-92b-5p gene (miRBase Accession No. MIMAT0004792) shown inSEQ ID NO: 176, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-92b” (miRBase Accession No. MI0003560, SEQ IDNO: 435) having a hairpin-like structure is known as a precursor of“hsa-miR-92b-5p”.

The term “hsa-miR-3679-5p gene” or “hsa-miR-3679-5p” used hereinincludes the hsa-miR-3679-5p gene (miRBase Accession No. MIMAT0018104)shown in SEQ ID NO: 177, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Creighton C J et al., 2010, PLoS One, Vol. 5, e9637. Also,“hsa-mir-3679” (miRBase Accession No. MI0016080, SEQ ID NO: 436) havinga hairpin-like structure is known as a precursor of “hsa-miR-3679-5p”.

The term “hsa-miR-4792 gene” or “hsa-miR-4792” used herein includes thehsa-miR-4792 gene (miRBase Accession No. MIMAT0019964) shown in SEQ IDNO: 178, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4792” (miRBase Accession No. MI0017439, SEQ ID NO: 437) havinga hairpin-like structure is known as a precursor of “hsa-miR-4792”.

The term “hsa-miR-3656 gene” or “hsa-miR-3656” used herein includes thehsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) shown in SEQ IDNO: 179, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inMeiri E et al., 2010, Nucleic Acids Res, Vol. 38, p. 6234-6246. Also,“hsa-mir-3656” (miRBase Accession No. MI0016056, SEQ ID NO: 438) havinga hairpin-like structure is known as a precursor of “hsa-miR-3656”.

The term “hsa-miR-92a-2-5p gene” or “hsa-miR-92a-2-5p” used hereinincludes the hsa-miR-92a-2-5p gene (miRBase Accession No. MIMAT0004508)shown in SEQ ID NO: 180, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Mourelatos Z et al., 2002, Genes Dev, Vol. 16, p. 720-728.Also, “hsa-mir-92a-2” (miRBase Accession No. MI0000094, SEQ ID NO: 439)having a hairpin-like structure is known as a precursor of“hsa-miR-92a-2-5p”.

The term “hsa-miR-4466 gene” or “hsa-miR-4466” used herein includes thehsa-miR-4466 gene (miRBase Accession No. MIMAT0018993) shown in SEQ IDNO: 181, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4466”(miRBase Accession No. MI0016817, SEQ ID NO: 440) having a hairpin-likestructure is known as a precursor of “hsa-miR-4466”.

The term “hsa-miR-4513 gene” or “hsa-miR-4513” used herein includes thehsa-miR-4513 gene (miRBase Accession No. MIMAT0019050) shown in SEQ IDNO: 182, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4513”(miRBase Accession No. MI0016879, SEQ ID NO: 441) having a hairpin-likestructure is known as a precursor of “hsa-miR-4513”.

The term “hsa-miR-6781-5p gene” or “hsa-miR-6781-5p” used hereinincludes the hsa-miR-6781-5p gene (miRBase Accession No. MIMAT0027462)shown in SEQ ID NO: 183, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6781” (miRBase Accession No. MI0022626, SEQ ID NO: 442)having a hairpin-like structure is known as a precursor of“hsa-miR-6781-5p”.

The term “hsa-miR-4649-5p gene” or “hsa-miR-4649-5p” used hereinincludes the hsa-miR-4649-5p gene (miRBase Accession No. MIMAT0019711)shown in SEQ ID NO: 184, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4649” (miRBase Accession No. MI0017276, SEQ ID NO: 443)having a hairpin-like structure is known as a precursor of“hsa-miR-4649-5p”.

The term “hsa-miR-6775-5p gene” or “hsa-miR-6775-5p” used hereinincludes the hsa-miR-6775-5p gene (miRBase Accession No. MIMAT0027450)shown in SEQ ID NO: 185, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6775” (miRBase Accession No. MI0022620, SEQ ID NO: 444)having a hairpin-like structure is known as a precursor of“hsa-miR-6775-5p”.

The term “hsa-miR-4651 gene” or “hsa-miR-4651” used herein includes thehsa-miR-4651 gene (miRBase Accession No. MIMAT0019715) shown in SEQ IDNO: 186, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4651” (miRBase Accession No. MI0017279, SEQ ID NO: 445) havinga hairpin-like structure is known as a precursor of “hsa-miR-4651”.

The term “hsa-miR-3195 gene” or “hsa-miR-3195” used herein includes thehsa-miR-3195 gene (miRBase Accession No. MIMAT0015079) shown in SEQ IDNO: 187, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3195”(miRBase Accession No. MI0014240, SEQ ID NO: 446) having a hairpin-likestructure is known as a precursor of “hsa-miR-3195”.

The term “hsa-miR-6726-5p gene” or “hsa-miR-6726-5p” used hereinincludes the hsa-miR-6726-5p gene (miRBase Accession No. MIMAT0027353)shown in SEQ ID NO: 188, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6726” (miRBase Accession No. MI0022571, SEQ ID NO: 447)having a hairpin-like structure is known as a precursor of“hsa-miR-6726-5p”.

The term “hsa-miR-6872-3p gene” or “hsa-miR-6872-3p” used hereinincludes the hsa-miR-6872-3p gene (miRBase Accession No. MIMAT0027645)shown in SEQ ID NO: 189, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6872” (miRBase Accession No. MI0022719, SEQ ID NO: 448)having a hairpin-like structure is known as a precursor of“hsa-miR-6872-3p”.

The term “hsa-miR-371a-5p gene” or “hsa-miR-371a-5p” used hereinincludes the hsa-miR-371a-5p gene (miRBase Accession No. MIMAT0004687)shown in SEQ ID NO: 190, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Suh M R et al., 2004, Dev Biol, Vol. 270, p. 488-498. Also,“hsa-mir-371a” (miRBase Accession No. MI0000779, SEQ ID NO: 449) havinga hairpin-like structure is known as a precursor of “hsa-miR-371a-5p”.

The term “hsa-miR-6777-5p gene” or “hsa-miR-6777-5p” used hereinincludes the hsa-miR-6777-5p gene (miRBase Accession No. MIMAT0027454)shown in SEQ ID NO: 191, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6777” (miRBase Accession No. MI0022622, SEQ ID NO: 450)having a hairpin-like structure is known as a precursor of“hsa-miR-6777-5p”.

The term “hsa-miR-6789-5p gene” or “hsa-miR-6789-5p” used hereinincludes the hsa-miR-6789-5p gene (miRBase Accession No. MIMAT0027478)shown in SEQ ID NO: 192, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6789” (miRBase Accession No. MI0022634, SEQ ID NO: 451)having a hairpin-like structure is known as a precursor of“hsa-miR-6789-5p”.

The term “hsa-miR-7975 gene” or “hsa-miR-7975” used herein includes thehsa-miR-7975 gene (miRBase Accession No. MIMAT0031178) shown in SEQ IDNO: 193, a homolog or an ortholog of a different organism species, andthe like. The gene can be obtained by a method described inVelthut-Meikas A et al., 2013, Mol Endocrinol, Vol. 27, p. 1128-1141.Also, “hsa-mir-7975” (miRBase Accession No. MI0025751, SEQ ID NO: 452)having a hairpin-like structure is known as a precursor of“hsa-miR-7975”.

The term “hsa-miR-6821-5p gene” or “hsa-miR-6821-5p” used hereinincludes the hsa-miR-6821-5p gene (miRBase Accession No. MIMAT0027542)shown in SEQ ID NO: 194, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6821” (miRBase Accession No. MI0022666, SEQ ID NO: 453)having a hairpin-like structure is known as a precursor of“hsa-miR-6821-5p”.

The term “hsa-miR-4534 gene” or “hsa-miR-4534” used herein includes thehsa-miR-4534 gene (miRBase Accession No. MIMAT0019073) shown in SEQ IDNO: 195, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4534”(miRBase Accession No. MI0016901, SEQ ID NO: 454) having a hairpin-likestructure is known as a precursor of “hsa-miR-4534”.

The term “hsa-miR-619-5p gene” or “hsa-miR-619-5p” used herein includesthe hsa-miR-619-5p gene (miRBase Accession No. MIMAT0026622) shown inSEQ ID NO: 196, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCummins J M et al., 2006, Proc Natl Acad Sci USA, Vol. 103, p.3687-3692. Also, “hsa-mir-619” (miRBase Accession No. MI0003633, SEQ IDNO: 455) having a hairpin-like structure is known as a precursor of“hsa-miR-619-5p”.

The term “hsa-miR-7107-5p gene” or “hsa-miR-7107-5p” used hereinincludes the hsa-miR-7107-5p gene (miRBase Accession No. MIMAT0028111)shown in SEQ ID NO: 197, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-7107” (miRBase Accession No. MI0022958, SEQ ID NO: 456)having a hairpin-like structure is known as a precursor of“hsa-miR-7107-5p”.

The term “hsa-miR-1228-3p gene” or “hsa-miR-1228-3p” used hereinincludes the hsa-miR-1228-3p gene (miRBase Accession No. MIMAT0005583)shown in SEQ ID NO: 198, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1228” (miRBase Accession No. MI0006318, SEQ ID NO: 457)having a hairpin-like structure is known as a precursor of“hsa-miR-1228-3p”.

The term “hsa-miR-6774-5p gene” or “hsa-miR-6774-5p” used hereinincludes the hsa-miR-6774-5p gene (miRBase Accession No. MIMAT0027448)shown in SEQ ID NO: 199, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6774” (miRBase Accession No. MI0022619, SEQ ID NO: 458)having a hairpin-like structure is known as a precursor of“hsa-miR-6774-5p”.

The term “hsa-miR-6805-5p gene” or “hsa-miR-6805-5p” used hereinincludes the hsa-miR-6805-5p gene (miRBase Accession No. MIMAT0027510)shown in SEQ ID NO: 200, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6805” (miRBase Accession No. MI0022650, SEQ ID NO: 459)having a hairpin-like structure is known as a precursor of“hsa-miR-6805-5p”.

The term “hsa-miR-23a-3p gene” or “hsa-miR-23a-3p” used herein includesthe hsa-miR-23a-3p gene (miRBase Accession No. MIMAT0000078) shown inSEQ ID NO: 201, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLagos-Quintana M et al., 2001, Science, Vol. 294, p. 853-858. Also,“hsa-mir-23a” (miRBase Accession No. MI0000079, SEQ ID NO: 460) having ahairpin-like structure is known as a precursor of “hsa-miR-23a-3p”.

The term “hsa-miR-4665-5p gene” or “hsa-miR-4665-5p” used hereinincludes the hsa-miR-4665-5p gene (miRBase Accession No. MIMAT0019739)shown in SEQ ID NO: 202, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4665” (miRBase Accession No. MI0017295, SEQ ID NO: 461)having a hairpin-like structure is known as a precursor of“hsa-miR-4665-5p”.

The term “hsa-miR-4505 gene” or “hsa-miR-4505” used herein includes thehsa-miR-4505 gene (miRBase Accession No. MIMAT0019041) shown in SEQ IDNO: 203, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4505”(miRBase Accession No. MI0016868, SEQ ID NO: 462) having a hairpin-likestructure is known as a precursor of “hsa-miR-4505”.

The term “hsa-miR-4638-5p gene” or “hsa-miR-4638-5p” used hereinincludes the hsa-miR-4638-5p gene (miRBase Accession No. MIMAT0019695)shown in SEQ ID NO: 204, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4638” (miRBase Accession No. MI0017265, SEQ ID NO: 463)having a hairpin-like structure is known as a precursor of“hsa-miR-4638-5p”.

The term “hsa-miR-24-3p gene” or “hsa-miR-24-3p” used herein includesthe hsa-miR-24-3p gene (miRBase Accession No. MIMAT0000080) shown in SEQID NO: 205, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLagos-Quintana M et al., 2001, Science, Vol. 294, p. 853-858. Also,“hsa-mir-24-1 and hsa-mir-24-2” (miRBase Accession Nos. MI0000080 andMI0000081, SEQ ID NOs: 464 and 465) having a hairpin-like structure areknown as a precursor of “hsa-miR-24-3p”.

The term “hsa-miR-3135b gene” or “hsa-miR-3135b” used herein includesthe hsa-miR-3135b gene (miRBase Accession No. MIMAT0018985) shown in SEQID NO: 206, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e27. Also, “hsa-mir-3135b”(miRBase Accession No. MI0016809, SEQ ID NO: 466) having a hairpin-likestructure is known as a precursor of “hsa-miR-3135b”.

The term “hsa-miR-4745-5p gene” or “hsa-miR-4745-5p” used hereinincludes the hsa-miR-4745-5p gene (miRBase Accession No. MIMAT0019878)shown in SEQ ID NO: 207, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4745” (miRBase Accession No. MI0017384, SEQ ID NO: 467)having a hairpin-like structure is known as a precursor of“hsa-miR-4745-5p”.

The term “hsa-miR-128-1-5p gene” or “hsa-miR-128-1-5p” used hereinincludes the hsa-miR-128-1-5p gene (miRBase Accession No. MIMAT0026477)shown in SEQ ID NO: 208, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Lagos-Quintana M et al., 2002, Curr Biol, Vol. 12, p.735-739. Also, “hsa-mir-128-1” (miRBase Accession No. MI0000447, SEQ IDNO: 468) having a hairpin-like structure is known as a precursor of“hsa-miR-128-1-5p”.

The term “hsa-miR-4476 gene” or “hsa-miR-4476” used herein includes thehsa-miR-4476 gene (miRBase Accession No. MIMAT0019003) shown in SEQ IDNO: 209, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4476”(miRBase Accession No. MI0016828, SEQ ID NO: 469) having a hairpin-likestructure is known as a precursor of “hsa-miR-4476”.

The term “hsa-miR-4687-3p gene” or “hsa-miR-4687-3p” used hereinincludes the hsa-miR-4687-3p gene (miRBase Accession No. MIMAT0019775)shown in SEQ ID NO: 210, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4687” (miRBase Accession No. MI0017319, SEQ ID NO: 470)having a hairpin-like structure is known as a precursor of“hsa-miR-4687-3p”.

The term “hsa-miR-3665 gene” or “hsa-miR-3665” used herein includes thehsa-miR-3665 gene (miRBase Accession No. MIMAT0018087) shown in SEQ IDNO: 211, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inXie X et al., 2005, Nature, Vol. 434, p. 338-345. Also, “hsa-mir-3665”(miRBase Accession No. MI0016066, SEQ ID NO: 471) having a hairpin-likestructure is known as a precursor of “hsa-miR-3665”.

The term “hsa-miR-6806-5p gene” or “hsa-miR-6806-5p” used hereinincludes the hsa-miR-6806-5p gene (miRBase Accession No. MIMAT0027512)shown in SEQ ID NO: 212, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6806” (miRBase Accession No. MI0022651, SEQ ID NO: 472)having a hairpin-like structure is known as a precursor of“hsa-miR-6806-5p”.

The term “hsa-miR-3937 gene” or “hsa-miR-3937” used herein includes thehsa-miR-3937 gene (miRBase Accession No. MIMAT0018352) shown in SEQ IDNO: 213, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inLiao J Y et al., 2010, PLoS One, Vol. 5, e10563. Also, “hsa-mir-3937”(miRBase Accession No. MI0016593, SEQ ID NO: 473) having a hairpin-likestructure is known as a precursor of “hsa-miR-3937”.

The term “hsa-miR-711 gene” or “hsa-miR-711” used herein includes thehsa-miR-711 gene (miRBase Accession No. MIMAT0012734) shown in SEQ IDNO: 214, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inArtzi S et al., 2008, BMC Bioinformatics, Vol. 9, p. 39. Also,“hsa-mir-711” (miRBase Accession No. MI0012488, SEQ ID NO: 474) having ahairpin-like structure is known as a precursor of “hsa-miR-711”

The term “hsa-miR-3141 gene” or “hsa-miR-3141” used herein includes thehsa-miR-3141 gene (miRBase Accession No. MIMAT0015010) shown in SEQ IDNO: 215, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3141”(miRBase Accession No. MI0014165, SEQ ID NO: 475) having a hairpin-likestructure is known as a precursor of “hsa-miR-3141”.

The term “hsa-miR-3188 gene” or “hsa-miR-3188” used herein includes thehsa-miR-3188 gene (miRBase Accession No. MIMAT0015070) shown in SEQ IDNO: 216, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inStark M S et al., 2010, PLoS One, Vol. 5, e9685. Also, “hsa-mir-3188”(miRBase Accession No. MI0014232, SEQ ID NO: 476) having a hairpin-likestructure is known as a precursor of “hsa-miR-3188”.

The term “hsa-miR-4281 gene” or “hsa-miR-4281” used herein includes thehsa-miR-4281 gene (miRBase Accession No. MIMAT0016907) shown in SEQ IDNO: 217, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4281”(miRBase Accession No. MI0015885, SEQ ID NO: 477) having a hairpin-likestructure is known as a precursor of “hsa-miR-4281”.

The term “hsa-miR-5196-5p gene” or “hsa-miR-5196-5p” used hereinincludes the hsa-miR-5196-5p gene (miRBase Accession No. MIMAT0021128)shown in SEQ ID NO: 218, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Schotte D et al., 2011, Leukemia, Vol. 25, p. 1389-1399.Also, “hsa-mir-5196” (miRBase Accession No. MI0018175, SEQ ID NO: 478)having a hairpin-like structure is known as a precursor of“hsa-miR-5196-5p”.

The term “hsa-miR-6880-5p gene” or “hsa-miR-6880-5p” used hereinincludes the hsa-miR-6880-5p gene (miRBase Accession No. MIMAT0027660)shown in SEQ ID NO: 219, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6880” (miRBase Accession No. MI0022727, SEQ ID NO: 479)having a hairpin-like structure is known as a precursor of“hsa-miR-6880-5p”.

The term “hsa-miR-3960 gene” or “hsa-miR-3960” used herein includes thehsa-miR-3960 gene (miRBase Accession No. MIMAT0019337) shown in SEQ IDNO: 220, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inHu R et al., 2011, J Biol Chem, Vol. 286, p. 12328-12339. Also,“hsa-mir-3960” (miRBase Accession No. MI0016964, SEQ ID NO: 480) havinga hairpin-like structure is known as a precursor of “hsa-miR-3960”.

The term “hsa-miR-3648 gene” or “hsa-miR-3648” used herein includes thehsa-miR-3648 gene (miRBase Accession No. MIMAT0018068) shown in SEQ IDNO: 221, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inMeiri E et al., 2010, Nucleic Acids Res, Vol. 38, p. 6234-6246. Also,“hsa-mir-3648-1 and hsa-miR-3648-2” (miRBase Accession Nos. MI0016048and MI0031512, SEQ ID NOs: 481 and 482) having a hairpin-like structureare known as a precursor of “hsa-miR-3648”.

The term “hsa-miR-6721-5p gene” or “hsa-miR-6721-5p” used hereinincludes the hsa-miR-6721-5p gene (miRBase Accession No. MIMAT0025852)shown in SEQ ID NO: 222, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Li Y et al., 2012, Gene, Vol. 497, p. 330-335. Also,“hsa-mir-6721” (miRBase Accession No. MI0022556, SEQ ID NO: 483) havinga hairpin-like structure is known as a precursor of “hsa-miR-6721-5p”.

The term “hsa-miR-4492 gene” or “hsa-miR-4492” used herein includes thehsa-miR-4492 gene (miRBase Accession No. MIMAT0019027) shown in SEQ IDNO: 223, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4492”(miRBase Accession No. MI0016854, SEQ ID NO: 484) having a hairpin-likestructure is known as a precursor of “hsa-miR-4492”.

The term “hsa-miR-744-5p gene” or “hsa-miR-744-5p” used herein includesthe hsa-miR-744-5p gene (miRBase Accession No. MIMAT0004945) shown inSEQ ID NO: 224, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inBerezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also,“hsa-mir-744” (miRBase Accession No. MI0005559, SEQ ID NO: 485) having ahairpin-like structure is known as a precursor of “hsa-miR-744-5p”.

The term “hsa-miR-7704 gene” or “hsa-miR-7704” used herein includes thehsa-miR-7704 gene (miRBase Accession No. MIMAT0030019) shown in SEQ IDNO: 225, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inSwaminathan S et al., 2013, Biochem Biophys Res Commun, Vol. 434, p.228-234. Also, “hsa-mir-7704” (miRBase Accession No. MI0025240, SEQ IDNO: 486) having a hairpin-like structure is known as a precursor of“hsa-miR-7704”.

The term “hsa-miR-4749-5p gene” or “hsa-miR-4749-5p” used hereinincludes the hsa-miR-4749-5p gene (miRBase Accession No. MIMAT0019885)shown in SEQ ID NO: 226, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Persson H et al., 2011, Cancer Res, Vol. 71, p. 78-86.Also, “hsa-mir-4749” (miRBase Accession No. MI0017388, SEQ ID NO: 487)having a hairpin-like structure is known as a precursor of“hsa-miR-4749-5p”.

The term “hsa-miR-6794-5p gene” or “hsa-miR-6794-5p” used hereinincludes the hsa-miR-6794-5p gene (miRBase Accession No. MIMAT0027488)shown in SEQ ID NO: 227, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6794” (miRBase Accession No. MI0022639, SEQ ID NO: 488)having a hairpin-like structure is known as a precursor of“hsa-miR-6794-5p”.

The term “hsa-miR-6511a-5p gene” or “hsa-miR-6511a-5p” used hereinincludes the hsa-miR-6511a-5p gene (miRBase Accession No. MIMAT0025478)shown in SEQ ID NO: 228, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Joyce C E et al., 2011, Hum Mol Genet, Vol. 20, p.4025-4040. Also, “hsa-mir-6511a-1, hsa-mir-6511a-2, hsa-mir-6511a-3 andhsa-mir-6511a-4” (miRBase Accession Nos. MI0022223, MI0023564, MI0023565and MI0023566, SEQ ID NOs: 489, 490, 491 and 492) having a hairpin-likestructure are known as a precursor of “hsa-miR-6511a-5p”.

The term “hsa-miR-6824-5p gene” or “hsa-miR-6824-5p” used hereinincludes the hsa-miR-6824-5p gene (miRBase Accession No. MIMAT0027548)shown in SEQ ID NO: 229, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6824” (miRBase Accession No. MI0022669, SEQ ID NO: 493)having a hairpin-like structure is known as a precursor of“hsa-miR-6824-5p”.

The term “hsa-miR-762 gene” or “hsa-miR-762” used herein includes thehsa-miR-762 gene (miRBase Accession No. MIMAT0010313) shown in SEQ IDNO: 230, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inBerezikov E et al., 2006, Genome Res, Vol. 16, p. 1289-1298. Also,“hsa-mir-762” (miRBase Accession No. MI0003892, SEQ ID NO: 494) having ahairpin-like structure is known as a precursor of “hsa-miR-762”.

The term “hsa-miR-6836-3p gene” or “hsa-miR-6836-3p” used hereinincludes the hsa-miR-6836-3p gene (miRBase Accession No. MIMAT0027575)shown in SEQ ID NO: 231, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6836” (miRBase Accession No. MI0022682, SEQ ID NO: 495)having a hairpin-like structure is known as a precursor of“hsa-miR-6836-3p”.

The term “hsa-miR-6727-5p gene” or “hsa-miR-6727-5p” used hereinincludes the hsa-miR-6727-5p gene (miRBase Accession No. MIMAT0027355)shown in SEQ ID NO: 232, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6727” (miRBase Accession No. MI0022572, SEQ ID NO: 496)having a hairpin-like structure is known as a precursor of“hsa-miR-6727-5p”.

The term “hsa-miR-4739 gene” or “hsa-miR-4739” used herein includes thehsa-miR-4739 gene (miRBase Accession No. MIMAT0019868) shown in SEQ IDNO: 233, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4739” (miRBase Accession No. MI0017377, SEQ ID NO: 497) havinga hairpin-like structure is known as a precursor of “hsa-miR-4739”.

The term “hsa-miR-7977 gene” or “hsa-miR-7977” used herein includes thehsa-miR-7977 gene (miRBase Accession No. MIMAT0031180) shown in SEQ IDNO: 234, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inVelthut-Meikas A et al., 2013, Mol Endocrinol, Vol. 27, p. 1128-1141.Also, “hsa-mir-7977” (miRBase Accession No. MI0025753, SEQ ID NO: 498)having a hairpin-like structure is known as a precursor of“hsa-miR-7977”.

The term “hsa-miR-4484 gene” or “hsa-miR-4484” used herein includes thehsa-miR-4484 gene (miRBase Accession No. MIMAT0019018) shown in SEQ IDNO: 235, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4484”(miRBase Accession No. MI0016845, SEQ ID NO: 499) having a hairpin-likestructure is known as a precursor of “hsa-miR-4484”.

The term “hsa-miR-6515-3p gene” or “hsa-miR-6515-3p” used hereinincludes the hsa-miR-6515-3p gene (miRBase Accession No. MIMAT0025487)shown in SEQ ID NO: 236, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Joyce C E et al., 2011, Hum Mol Genet, Vol. 20, p.4025-4040. Also, “hsa-mir-6515” (miRBase Accession No. MI0022227, SEQ IDNO: 500) having a hairpin-like structure is known as a precursor of“hsa-miR-6515-3p”.

The term “hsa-miR-373-5p gene” or “hsa-miR-373-5p” used herein includesthe hsa-miR-373-5p gene (miRBase Accession No. MIMAT0000725) shown inSEQ ID NO: 237, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inSuh M R et al., 2004, Dev Biol, Vol. 270, p. 488-498. Also,“hsa-mir-373” (miRBase Accession No. MI0000781, SEQ ID NO: 501) having ahairpin-like structure is known as a precursor of “hsa-miR-373-5p”.

The term “hsa-miR-4258 gene” or “hsa-miR-4258” used herein includes thehsa-miR-4258 gene (miRBase Accession No. MIMAT0016879) shown in SEQ IDNO: 238, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4258”(miRBase Accession No. MI0015857, SEQ ID NO: 502) having a hairpin-likestructure is known as a precursor of “hsa-miR-4258”.

The term “hsa-miR-4674 gene” or “hsa-miR-4674” used herein includes thehsa-miR-4674 gene (miRBase Accession No. MIMAT0019756) shown in SEQ IDNO: 239, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4674” (miRBase Accession No. MI0017305, SEQ ID NO: 503) havinga hairpin-like structure is known as a precursor of “hsa-miR-4674”.

The term “hsa-miR-3180 gene” or “hsa-miR-3180” used herein includes thehsa-miR-3180 gene (miRBase Accession No. MIMAT0018178) shown in SEQ IDNO: 240, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inCreighton C J et al., 2010, PLoS One, Vol. 5, e9637. Also,“hsa-mir-3180-4 and hsa-mir-3180-5” (miRBase Accession Nos. MI0016408and MI0016409, SEQ ID NOs: 504 and 505) having a hairpin-like structureare known as a precursor of “hsa-miR-3180”.

The term “hsa-miR-6076 gene” or “hsa-miR-6076” used herein includes thehsa-miR-6076 gene (miRBase Accession No. MIMAT0023701) shown in SEQ IDNO: 241, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inVoellenkle C et al., 2012, RNA, VOL. 18, p. 472-484. Also,“hsa-mir-6076” (miRBase Accession No. MI0020353, SEQ ID NO: 506) havinga hairpin-like structure is known as a precursor of “hsa-miR-6076”.

The term “hsa-miR-1238-5p gene” or “hsa-miR-1238-5p” used hereinincludes the hsa-miR-1238-5p gene (miRBase Accession No. MIMAT0022947)shown in SEQ ID NO: 242, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Berezikov E et al., 2007, Mol Cell, Vol. 28, p. 328-336.Also, “hsa-mir-1238” (miRBase Accession No. MI0006328, SEQ ID NO: 507)having a hairpin-like structure is known as a precursor of“hsa-miR-1238-5p”.

The term “hsa-miR-4463 gene” or “hsa-miR-4463” used herein includes thehsa-miR-4463 gene (miRBase Accession No. MIMAT0018987) shown in SEQ IDNO: 243, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4463”(miRBase Accession No. MI0016811, SEQ ID NO: 508) having a hairpin-likestructure is known as a precursor of “hsa-miR-4463”.

The term “hsa-miR-4486 gene” or “hsa-miR-4486” used herein includes thehsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) shown in SEQ IDNO: 244, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inJima D D et al., 2010, Blood, Vol. 116, e118-e127. Also, “hsa-mir-4486”(miRBase Accession No. MI0016847, SEQ ID NO: 509) having a hairpin-likestructure is known as a precursor of “hsa-miR-4486”.

The term “hsa-miR-4730 gene” or “hsa-miR-4730” used herein includes thehsa-miR-4730 gene (miRBase Accession No. MIMAT0019852) shown in SEQ IDNO: 245, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4730” (miRBase Accession No. MI0017367, SEQ ID NO: 510) havinga hairpin-like structure is known as a precursor of “hsa-miR-4730”.

The term “hsa-miR-6766-3p gene” or “hsa-miR-6766-3p” used hereinincludes the hsa-miR-6766-3p gene (miRBase Accession No. MIMAT0027433)shown in SEQ ID NO: 246, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6766” (miRBase Accession No. MI0022611, SEQ ID NO: 511)having a hairpin-like structure is known as a precursor of“hsa-miR-6766-3p”.

The term “hsa-miR-4286 gene” or “hsa-miR-4286” used herein includes thehsa-miR-4286 gene (miRBase Accession No. MIMAT0016916) shown in SEQ IDNO: 247, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inGoff L A et al., 2009, PLoS One, Vol. 4, e7192. Also, “hsa-mir-4286”(miRBase Accession No. MI0015894, SEQ ID NO: 512) having a hairpin-likestructure is known as a precursor of “hsa-miR-4286”.

The term “hsa-miR-6511a-5p gene” or “hsa-miR-6511a-5p” used hereinincludes the hsa-miR-6511a-5p gene (miRBase Accession No. MIMAT0025478)shown in SEQ ID NO: 248, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Joyce C E et al., 2011, Hum Mol Genet, Vol. 20, p.4025-4040. Also, “hsa-mir-6511a-1, hsa-mir-6511a-2, hsa-mir-6511a-3 andhsa-mir-6511a-4” (miRBase Accession Nos. MI0022223, MI0023564, MI0023565and MI0023566, SEQ ID NOs: 513, 514, 515 and 516) having a hairpin-likestructure are known as a precursor of “hsa-miR-6511a-5p”.

The term “hsa-miR-4739 gene” or “hsa-miR-4739” used herein includes thehsa-miR-4739 gene (miRBase Accession No. MIMAT0019868) shown in SEQ IDNO: 249, a homolog or an ortholog thereof of a different organismspecies, and the like. The gene can be obtained by a method described inPersson H et al., 2011, Cancer Res, Vol. 71, p. 78-86. Also,“hsa-mir-4739” (miRBase Accession No. MI0017377, SEQ ID NO: 517) havinga hairpin-like structure is known as a precursor of “hsa-miR-4739”.

The term “hsa-miR-6749-5p gene” or “hsa-miR-6749-5p” used hereinincludes the hsa-miR-6749-5p gene (miRBase Accession No. MIMAT0027398)shown in SEQ ID NO: 250, a homolog or an ortholog thereof of a differentorganism species, and the like. The gene can be obtained by a methoddescribed in Ladewig E et al., 2012, Genome Res, Vol. 22, p. 1634-1645.Also, “hsa-mir-6749” (miRBase Accession No. MI0022594, SEQ ID NO: 518)having a hairpin-like structure is known as a precursor of“hsa-miR-6749-5p”.

A mature miRNA may become a variant, due to a cleavage whereby theresulting sequence is shorter or longer by one to several flankingnucleotides, or due to substitution of nucleotides, when cut out as themature miRNA from its RNA precursor having a hairpin-like structure.This variant is called isomiR (Morin R D. et al., 2008, Genome Res.,Vol. 18, p. 610-621). The miRBase Release 20 shows the nucleotidesequences represented by SEQ ID NOs: 1 to 250 as well as a large numberof the nucleotide sequence variants and fragments represented by SEQ IDNOs: 519 to 812, called isomiRs. These variants can also be obtained asmiRNAs having a nucleotide sequence represented by any of SEQ ID NOs: 1to 250. Specifically, among the variants of polynucleotides consistingof the nucleotide sequence represented by any of SEQ ID NOs: 2, 3, 6, 7,8, 11, 12, 13, 15, 19, 20, 25, 26, 27, 29, 31, 32, 37, 44, 45, 46, 47,48, 49, 51, 52, 53, 54, 55, 56, 57, 59, 60, 61, 62, 63, 71, 72, 73, 74,76, 77, 78, 79, 83, 84, 86, 87, 88, 89, 90, 92, 94, 98, 102, 105, 106,108, 111, 112, 113, 114, 116, 117, 118, 122, 123, 124, 128, 129, 133,134, 135, 136, 137, 140, 141, 145, 146, 147, 148, 149, 150, 151, 153,154, 155, 157, 158, 159, 160, 161, 162, 163, 166, 167, 168, 169, 176,177, 178, 179, 180, 181, 182, 184, 186, 187, 190, 193, 196, 198, 201,202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 214, 215, 216, 217,218, 220, 221, 222, 223, 224, 226, 228, 233, 235, 236, 237, 239, 240,243, 244, 245, 247, 248, and 249 or a nucleotide sequence derived fromthe nucleotide sequence by the replacement of u with t according to thepresent invention, examples of the longest variants registered inmiRBase Release 20 include polynucleotides represented by SEQ ID NOs:519, 521, 523, 525, 527, 529, 531, 533, 535, 537, 539, 541, 543, 545,547, 549, 551, 553, 555, 557, 559, 561, 563, 565, 567, 569, 571, 573,575, 577, 579, 581, 583, 585, 587, 589, 591, 593, 595, 597, 599, 601,603, 605, 607, 609, 611, 613, 615, 617, 619, 621, 623, 625, 627, 629,631, 633, 635, 637, 639, 641, 643, 645, 647, 649, 651, 653, 655, 657,659, 661, 663, 665, 667, 669, 671, 673, 675, 677, 679, 681, 683, 685,687, 689, 691, 693, 695, 697, 699, 701, 703, 705, 707, 709, 711, 713,715, 717, 719, 721, 723, 725, 727, 729, 731, 733, 735, 737, 739, 741,743, 745, 747, 749, 751, 753, 755, 757, 759, 761, 763, 765, 767, 769,771, 773, 775, 777, 779, 781, 783, 785, 787, 789, 791, 793, 795, 797,799, 801, 803, 805, 807, 809, and 811, respectively. Also, among thevariants of polynucleotides consisting of a nucleotide sequencerepresented by any of SEQ ID NOs: 2, 3, 6, 7, 8, 11, 12, 13, 15, 19, 20,25, 26, 27, 29, 31, 32, 37, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55,56, 57, 59, 60, 61, 62, 63, 71, 72, 73, 74, 76, 77, 78, 79, 83, 84, 86,87, 88, 89, 90, 92, 94, 98, 102, 105, 106, 108, 111, 112, 113, 114, 116,117, 118, 122, 123, 124, 128, 129, 133, 134, 135, 136, 137, 140, 141,145, 146, 147, 148, 149, 150, 151, 153, 154, 155, 157, 158, 159, 160,161, 162, 163, 166, 167, 168, 169, 176, 177, 178, 179, 180, 181, 182,184, 186, 187, 190, 193, 196, 198, 201, 202, 203, 204, 205, 206, 207,208, 209, 210, 211, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224,226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249or a nucleotide sequence derived from the nucleotide sequence by thereplacement of u with t according to the present invention, examples ofshortest variants registered in the miRBase Release 20 includepolynucleotides having sequences represented by SEQ ID NOs: 520, 522,524, 526, 528, 530, 532, 534, 536, 538, 540, 542, 544, 546, 548, 550,552, 554, 556, 558, 560, 562, 564, 566, 568, 570, 572, 574, 576, 578,580, 582, 584, 586, 588, 590, 592, 594, 596, 598, 600, 602, 604, 606,608, 610, 612, 614, 616, 618, 620, 622, 624, 626, 628, 630, 632, 634,636, 638, 640, 642, 644, 646, 648, 650, 652, 654, 656, 658, 660, 662,664, 666, 668, 670, 672, 674, 676, 678, 680, 682, 684, 686, 688, 690,692, 694, 696, 698, 700, 702, 704, 706, 708, 710, 712, 714, 716, 718,720, 722, 724, 726, 728, 730, 732, 734, 736, 738, 740, 742, 744, 746,748, 750, 752, 754, 756, 758, 760, 762, 764, 766, 768, 770, 772, 774,776, 778, 780, 782, 784, 786, 788, 790, 792, 794, 796, 798, 800, 802,804, 806, 808, 810, and 812, respectively. In addition to these variantsand fragments, examples thereof include a large number of isomiRpolynucleotides of SEQ ID NOs: 2, 3, 6, 7, 8, 11, 12, 13, 15, 19, 20,25, 26, 27, 29, 31, 32, 37, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55,56, 57, 59, 60, 61, 62, 63, 71, 72, 73, 74, 76, 77, 78, 79, 83, 84, 86,87, 88, 89, 90, 92, 94, 98, 102, 105, 106, 108, 111, 112, 113, 114, 116,117, 118, 122, 123, 124, 128, 129, 133, 134, 135, 136, 137, 140, 141,145, 146, 147, 148, 149, 150, 151, 153, 154, 155, 157, 158, 159, 160,161, 162, 163, 166, 167, 168, 169, 176, 177, 178, 179, 180, 181, 182,184, 186, 187, 190, 193, 196, 198, 201, 202, 203, 204, 205, 206, 207,208, 209, 210, 211, 214, 215, 216, 217, 218, 220, 221, 222, 223, 224,226, 228, 233, 235, 236, 237, 239, 240, 243, 244, 245, 247, 248, and 249registered in the miRBase. Examples of the polynucleotide comprising anucleotide sequence represented by any of SEQ ID NOs: 1 to 250 include apolynucleotide represented by any of SEQ ID NOs: 251 to 518, which aretheir respective precursors.

The names and miRBase Accession Nos. (registration numbers) of the genesrepresented by SEQ ID NOs: 1 to 812 are shown in Table 1.

As used herein, the term “capable of specifically binding” means thatthe nucleic acid probe or the primer used in the present invention bindsto a particular target nucleic acid and cannot substantially bind toother nucleic acids.

TABLE 1 miRBase SEQ ID NO: Gene name registration No. 1 hsa-miR-6784-5pMIMAT0027468 2 hsa-miR-1181 MIMAT0005826 3 hsa-miR-671-5p MIMAT0003880 4hsa-miR-6857-5p MIMAT0027614 5 hsa-miR-4276 MIMAT0016904 6hsa-miR-1914-3p MIMAT0007890 7 hsa-miR-149-3p MIMAT0004609 8hsa-miR-937-5p MIMAT0022938 9 hsa-miR-4675 MIMAT0019757 10hsa-miR-6795-5p MIMAT0027490 11 hsa-miR-4731-5p MIMAT0019853 12hsa-miR-5090 MIMAT0021082 13 hsa-miR-3620-5p MIMAT0022967 14hsa-miR-1343-5p MIMAT0027038 15 hsa-miR-6717-5p MIMAT0025846 16hsa-miR-6825-5p MIMAT0027550 17 hsa-miR-6738-5p MIMAT0027377 18hsa-miR-6769a-5p MIMAT0027438 19 hsa-miR-4728-5p MIMAT0019849 20hsa-miR-652-5p MIMAT0022709 21 hsa-miR-4257 MIMAT0016878 22hsa-miR-6785-5p MIMAT0027470 23 hsa-miR-7110-5p MIMAT0028117 24hsa-miR-6887-5p MIMAT0027674 25 hsa-miR-887-3p MIMAT0004951 26hsa-miR-1228-5p MIMAT0005582 27 hsa-miR-5572 MIMAT0022260 28hsa-miR-6782-5p MIMAT0027464 29 hsa-miR-4298 MIMAT0016852 30hsa-miR-6786-5p MIMAT0027472 31 hsa-miR-5010-5p MIMAT0021043 32hsa-miR-6087 MIMAT0023712 33 hsa-miR-6765-5p MIMAT0027430 34hsa-miR-6732-5p MIMAT0027365 35 hsa-miR-6787-5p MIMAT0027474 36hsa-miR-6737-5p MIMAT0027375 37 hsa-miR-128-2-5p MIMAT0031095 38hsa-miR-4270 MIMAT0016900 39 hsa-miR-6861-5p MIMAT0027623 40hsa-miR-6756-5p MIMAT0027412 41 hsa-miR-1229-5p MIMAT0022942 42hsa-miR-6891-5p MIMAT0027682 43 hsa-miR-6848-5p MIMAT0027596 44hsa-miR-1237-5p MIMAT0022946 45 hsa-miR-30c-1-3p MIMAT0004674 46hsa-miR-1233-5p MIMAT0022943 47 hsa-miR-211-3p MIMAT0022694 48hsa-miR-4758-5p MIMAT0019903 49 hsa-miR-614 MIMAT0003282 50hsa-miR-6746-5p MIMAT0027392 51 hsa-miR-1915-5p MIMAT0007891 52hsa-miR-4688 MIMAT0019777 53 hsa-miR-3917 MIMAT0018191 54 hsa-miR-5787MIMAT0023252 55 hsa-miR-4632-5p MIMAT0022977 56 hsa-miR-6126MIMAT0024599 57 hsa-miR-135a-3p MIMAT0004595 58 hsa-miR-8063MIMAT0030990 59 hsa-miR-5698 MIMAT0022491 60 hsa-miR-6089 MIMAT002371461 hsa-miR-498 MIMAT0002824 62 hsa-miR-296-3p MIMAT0004679 63hsa-miR-4419b MIMAT0019034 64 hsa-miR-6802-5p MIMAT0027504 65hsa-miR-6829-5p MIMAT0027558 66 hsa-miR-6803-5p MIMAT0027506 67hsa-miR-1199-5p MIMAT0031119 68 hsa-miR-6840-3p MIMAT0027583 69hsa-miR-6752-5p MIMAT0027404 70 hsa-miR-6798-5p MIMAT0027496 71hsa-miR-6131 MIMAT0024615 72 hsa-miR-4667-5p MIMAT0019743 73hsa-miR-6510-5p MIMAT0025476 74 hsa-miR-4690-5p MIMAT0019779 75hsa-miR-920 MIMAT0004970 76 hsa-miR-23b-3p MIMAT0000418 77 hsa-miR-4448MIMAT0018967 78 hsa-miR-2110 MIMAT0010133 79 hsa-miR-4706 MIMAT001980680 hsa-miR-7845-5p MIMAT0030420 81 hsa-miR-6808-5p MIMAT0027516 82hsa-miR-4447 MIMAT0018966 83 hsa-miR-6869-5p MIMAT0027638 84hsa-miR-1908-5p MIMAT0007881 85 hsa-miR-6729-5p MIMAT0027359 86hsa-miR-5195-3p MIMAT0021127 87 hsa-miR-638 MIMAT0003308 88 hsa-miR-6125MIMAT0024598 89 hsa-miR-3178 MIMAT0015055 90 hsa-miR-3196 MIMAT001508091 hsa-miR-8069 MIMAT0030996 92 hsa-miR-4723-5p MIMAT0019838 93hsa-miR-4746-3p MIMAT0019881 94 hsa-miR-4689 MIMAT0019778 95hsa-miR-6816-5p MIMAT0027532 96 hsa-miR-6757-5p MIMAT0027414 97hsa-miR-7109-5p MIMAT0028115 98 hsa-miR-6724-5p MIMAT0025856 99hsa-miR-1225-3p MIMAT0005573 100 hsa-miR-6875-5p MIMAT0027650 101hsa-miR-7108-5p MIMAT0028113 102 hsa-miR-4508 MIMAT0019045 103hsa-miR-6085 MIMAT0023710 104 hsa-miR-6779-5p MIMAT0027458 105hsa-miR-642a-3p MIMAT0020924 106 hsa-miR-4695-5p MIMAT0019788 107hsa-miR-7847-3p MIMAT0030422 108 hsa-miR-3197 MIMAT0015082 109hsa-miR-6769b-5p MIMAT0027620 110 hsa-miR-7641 MIMAT0029782 111hsa-miR-187-5p MIMAT0004561 112 hsa-miR-3185 MIMAT0015065 113hsa-miR-2861 MIMAT0013802 114 hsa-miR-3940-5p MIMAT0019229 115hsa-miR-1203 MIMAT0005866 116 hsa-miR-615-5p MIMAT0004804 117hsa-miR-4787-5p MIMAT0019956 118 hsa-miR-1343-3p MIMAT0019776 119hsa-miR-6813-5p MIMAT0027526 120 hsa-miR-1225-5p MIMAT0005572 121hsa-miR-602 MIMAT0003270 122 hsa-miR-4488 MIMAT0019022 123hsa-miR-125a-3p MIMAT0004602 124 hsa-miR-5100 MIMAT0022259 125hsa-miR-4294 MIMAT0016849 126 hsa-miR-1231 MIMAT0005586 127hsa-miR-6765-3p MIMAT0027431 128 hsa-miR-4442 MIMAT0018960 129hsa-miR-718 MIMAT0012735 130 hsa-miR-6780b-5p MIMAT0027572 131hsa-miR-6090 MIMAT0023715 132 hsa-miR-6845-5p MIMAT0027590 133hsa-miR-4741 MIMAT0019871 134 hsa-miR-4467 MIMAT0018994 135hsa-miR-4707-5p MIMAT0019807 136 hsa-miR-4271 MIMAT0016901 137hsa-miR-4673 MIMAT0019755 138 hsa-miR-3184-5p MIMAT0015064 139hsa-miR-1469 MIMAT0007347 140 hsa-miR-4640-5p MIMAT0019699 141hsa-miR-663a MIMAT0003326 142 hsa-miR-6791-5p MIMAT0027482 143hsa-miR-6826-5p MIMAT0027552 144 hsa-miR-4433b-3p MIMAT0030414 145hsa-miR-1915-3p MIMAT0007892 146 hsa-miR-4417 MIMAT0018929 147hsa-miR-4449 MIMAT0018968 148 hsa-miR-4707-3p MIMAT0019808 149hsa-miR-3180-3p MIMAT0015058 150 hsa-miR-5585-3p MIMAT0022286 151hsa-miR-1268a MIMAT0005922 152 hsa-miR-8072 MIMAT0030999 153hsa-miR-296-5p MIMAT0000690 154 hsa-miR-204-3p MIMAT0022693 155hsa-miR-4454 MIMAT0018976 156 hsa-miR-6722-3p MIMAT0025854 157hsa-miR-1290 MIMAT0005880 158 hsa-miR-3622a-5p MIMAT0018003 159hsa-miR-939-5p MIMAT0004982 160 hsa-miR-675-5p MIMAT0004284 161hsa-miR-3131 MIMAT0014996 162 hsa-miR-4648 MIMAT0019710 163hsa-miR-1268b MIMAT0018925 164 hsa-miR-6741-5p MIMAT0027383 165hsa-miR-6893-5p MIMAT0027686 166 hsa-miR-3162-5p MIMAT0015036 167hsa-miR-642b-3p MIMAT0018444 168 hsa-miR-4734 MIMAT0019859 169hsa-miR-150-3p MIMAT0004610 170 hsa-miR-8089 MIMAT0031016 171hsa-miR-6805-3p MIMAT0027511 172 hsa-miR-7113-3p MIMAT0028124 173hsa-miR-6850-5p MIMAT0027600 174 hsa-miR-6799-5p MIMAT0027498 175hsa-miR-6768-5p MIMAT0027436 176 hsa-miR-92b-5p MIMAT0004792 177hsa-miR-3679-5p MIMAT0018104 178 hsa-miR-4792 MIMAT0019964 179hsa-miR-3656 MIMAT0018076 180 hsa-miR-92a-2-5p MIMAT0004508 181hsa-miR-4466 MIMAT0018993 182 hsa-miR-4513 MIMAT0019050 183hsa-miR-6781-5p MIMAT0027462 184 hsa-miR-4649-5p MIMAT0019711 185hsa-miR-6775-5p MIMAT0027450 186 hsa-miR-4651 MIMAT0019715 187hsa-miR-3195 MIMAT0015079 188 hsa-miR-6726-5p MIMAT0027353 189hsa-miR-6872-3p MIMAT0027645 190 hsa-miR-371a-5p MIMAT0004687 191hsa-miR-6777-5p MIMAT0027454 192 hsa-miR-6789-5p MIMAT0027478 193hsa-miR-7975 MIMAT0031178 194 hsa-miR-6821-5p MIMAT0027542 195hsa-miR-4534 MIMAT0019073 196 hsa-miR-619-5p MIMAT0026622 197hsa-miR-7107-5p MIMAT0028111 198 hsa-miR-1228-3p MIMAT0005583 199hsa-miR-6774-5p MIMAT0027448 200 hsa-miR-6805-5p MIMAT0027510 201hsa-miR-23a-3p MIMAT0000078 202 hsa-miR-4665-5p MIMAT0019739 203hsa-miR-4505 MIMAT0019041 204 hsa-miR-4638-5p MIMAT0019695 205hsa-miR-24-3p MIMAT0000080 206 hsa-miR-3135b MIMAT0018985 207hsa-miR-4745-5p MIMAT0019878 208 hsa-miR-128-1-5p MIMAT0026477 209hsa-miR-4476 MIMAT0019003 210 hsa-miR-4687-3p MIMAT0019775 211hsa-miR-3665 MIMAT0018087 212 hsa-miR-6806-5p MIMAT0027512 213hsa-miR-3937 MIMAT0018352 214 hsa-miR-711 MIMAT0012734 215 hsa-miR-3141MIMAT0015010 216 hsa-miR-3188 MIMAT0015070 217 hsa-miR-4281 MIMAT0016907218 hsa-miR-5196-5p MIMAT0021128 219 hsa-miR-6880-5p MIMAT0027660 220hsa-miR-3960 MIMAT0019337 221 hsa-miR-3648 MIMAT0018068 222hsa-miR-6721-5p MIMAT0025852 223 hsa-miR-4492 MIMAT0019027 224hsa-miR-744-5p MIMAT0004945 225 hsa-miR-7704 MIMAT0030019 226hsa-miR-4749-5p MIMAT0019885 227 hsa-miR-6794-5p MIMAT0027488 228hsa-miR-6511a-5p MIMAT0025478 229 hsa-miR-6824-5p MIMAT0027548 230hsa-miR-762 MIMAT0010313 231 hsa-miR-6836-3p MIMAT0027575 232hsa-miR-6727-5p MIMAT0027355 233 hsa-miR-4739 MIMAT0019868 234hsa-miR-7977 MIMAT0031180 235 hsa-miR-4484 MIMAT0019018 236hsa-miR-6515-3p MIMAT0025487 237 hsa-miR-373-5p MIMAT0000725 238hsa-miR-4258 MIMAT0016879 239 hsa-miR-4674 MIMAT0019756 240 hsa-miR-3180MIMAT0018178 241 hsa-miR-6076 MIMAT0023701 242 hsa-miR-1238-5pMIMAT0022947 243 hsa-miR-4463 MIMAT0018987 244 hsa-miR-4486 MIMAT0019020245 hsa-miR-4730 MIMAT0019852 246 hsa-miR-6766-3p MIMAT0027433 247hsa-miR-4286 MIMAT0016916 248 hsa-miR-6511a-5p MIMAT0025478 249hsa-miR-4739 MIMAT0019868 250 hsa-miR-6749-5p MIMAT0027398 251hsa-mir-6784 MI0022629 252 hsa-mir-1181 MI0006274 253 hsa-mir-671MI0003760 254 hsa-mir-6857 MI0022703 255 hsa-mir-4276 MI0015882 256hsa-mir-1914 MI0008335 257 hsa-mir-149 MI0000478 258 hsa-mir-937MI0005759 259 hsa-mir-4675 MI0017306 260 hsa-mir-6795 MI0022640 261hsa-mir-4731 MI0017368 262 hsa-mir-5090 MI0017979 263 hsa-mir-3620MI0016011 264 hsa-mir-1343 MI0017320 265 hsa-mir-6717 MI0022551 266hsa-mir-6825 MI0022670 267 hsa-mir-6738 MI0022583 268 hsa-mir-6769aMI0022614 269 hsa-mir-4728 MI0017365 270 hsa-mir-652 MI0003667 271hsa-mir-4257 MI0015856 272 hsa-mir-6785 MI0022630 273 hsa-mir-7110MI0022961 274 hsa-mir-6887 MI0022734 275 hsa-mir-887 MI0005562 276hsa-mir-1228 MI0006318 277 hsa-mir-5572 MI0019117 278 hsa-mir-6782MI0022627 279 hsa-mir-4298 MI0015830 280 hsa-mir-6786 MI0022631 281hsa-mir-5010 MI0017878 282 hsa-mir-6087 MI0020364 283 hsa-mir-6765MI0022610 284 hsa-mir-6732 MI0022577 285 hsa-mir-6787 MI0022632 286hsa-mir-6737 MI0022582 287 hsa-mir-128-2 MI0000727 288 hsa-mir-4270MI0015878 289 hsa-mir-6861 MI0022708 290 hsa-mir-6756 MI0022601 291hsa-mir-1229 MI0006319 292 hsa-mir-6891 MI0022738 293 hsa-mir-6848MI0022694 294 hsa-mir-1237 MI0006327 295 hsa-mir-30c-1 MI0000736 296hsa-mir-1233-1 MI0006323 297 hsa-mir-1233-2 MI0015973 298 hsa-mir-211MI0000287 299 hsa-mir-4758 MI0017399 300 hsa-mir-614 MI0003627 301hsa-mir-6746 MI0022591 302 hsa-mir-1915 MI0008336 303 hsa-mir-4688MI0017321 304 hsa-mir-3917 MI0016423 305 hsa-mir-5787 MI0019797 306hsa-mir-4632 MI0017259 307 hsa-mir-6126 MI0021260 308 hsa-mir-135a-1MI0000452 309 hsa-mir-8063 MI0025899 310 hsa-mir-5698 MI0019305 311hsa-mir-6089-1 MI0020366 312 hsa-mir-6089-2 MI0023563 313 hsa-mir-498MI0003142 314 hsa-mir-296 MI0000747 315 hsa-mir-4419b MI0016861 316hsa-mir-6802 MI0022647 317 hsa-mir-6829 MI0022674 318 hsa-mir-6803MI0022648 319 hsa-mir-1199 MI0020340 320 hsa-mir-6840 MI0022686 321hsa-mir-6752 MI0022597 322 hsa-mir-6798 MI0022643 323 hsa-mir-6131MI0021276 324 hsa-mir-4667 MI0017297 325 hsa-mir-6510 MI0022222 326hsa-mir-4690 MI0017323 327 hsa-mir-920 MI0005712 328 hsa-mir-23bMI0000439 329 hsa-mir-4448 MI0016791 330 hsa-mir-2110 MI0010629 331hsa-mir-4706 MI0017339 332 hsa-mir-7845 MI0025515 333 hsa-mir-6808MI0022653 334 hsa-mir-4447 MI0016790 335 hsa-mir-6869 MI0022716 336hsa-mir-1908 MI0008329 337 hsa-mir-6729 MI0022574 338 hsa-mir-5195MI0018174 339 hsa-mir-638 MI0003653 340 hsa-mir-6125 MI0021259 341hsa-mir-3178 MI0014212 342 hsa-mir-3196 MI0014241 343 hsa-mir-8069-1MI0025905 344 hsa-mir-8069-2 MI0031519 345 hsa-mir-4723 MI0017359 346hsa-mir-4746 MI0017385 347 hsa-mir-4689 MI0017322 348 hsa-mir-6816MI0022661 349 hsa-mir-6757 MI0022602 350 hsa-mir-7109 MI0022960 351hsa-mir-6724-1 MI0022559 352 hsa-mir-6724-2 MI0031516 353 hsa-mir-6724-3MI0031517 354 hsa-mir-6724-4 MI0031518 355 hsa-mir-1225 MI0006311 356hsa-mir-6875 MI0022722 357 hsa-mir-7108 MI0022959 358 hsa-mir-4508MI0016872 359 hsa-mir-6085 MI0020362 360 hsa-mir-6779 MI0022624 361hsa-mir-642a MI0003657 362 hsa-mir-4695 MI0017328 363 hsa-mir-7847MI0025517 364 hsa-mir-3197 MI0014245 365 hsa-mir-6769b MI0022706 366hsa-mir-7641-1 MI0024975 367 hsa-mir-7641-2 MI0024976 368 hsa-mir-187MI0000274 369 hsa-mir-3185 MI0014227 370 hsa-mir-2861 MI0013006 371hsa-mir-3940 MI0016597 372 hsa-mir-1203 MI0006335 373 hsa-mir-615MI0003628 374 hsa-mir-4787 MI0017434 375 hsa-mir-1343 MI0017320 376hsa-mir-6813 MI0022658 377 hsa-mir-1225 MI0006311 378 hsa-mir-602MI0003615 379 hsa-mir-4488 MI0016849 380 hsa-mir-125a MI0000469 381hsa-mir-5100 MI0019116 382 hsa-mir-4294 MI0015827 383 hsa-mir-1231MI0006321 384 hsa-mir-6765 MI0022610 385 hsa-mir-4442 MI0016785 386hsa-mir-718 MI0012489 387 hsa-mir-6780b MI0022681 388 hsa-mir-6090MI0020367 389 hsa-mir-6845 MI0022691 390 hsa-mir-4741 MI0017379 391hsa-mir-4467 MI0016818 392 hsa-mir-4707 MI0017340 393 hsa-mir-4271MI0015879 394 hsa-mir-4673 MI0017304 395 hsa-mir-3184 MI0014226 396hsa-mir-1469 MI0007074 397 hsa-mir-4640 MI0017267 398 hsa-mir-663aMI0003672 399 hsa-mir-6791 MI0022636 400 hsa-mir-6826 MI0022671 401hsa-mir-4433b MI0025511 402 hsa-mir-1915 MI0008336 403 hsa-mir-4417MI0016753 404 hsa-mir-4449 MI0016792 405 hsa-mir-4707 MI0017340 406hsa-mir-3180-1 MI0014214 407 hsa-mir-3180-2 MI0014215 408 hsa-mir-3180-3MI0014217 409 hsa-mir-5585 MI0019142 410 hsa-mir-1268a MI0006405 411hsa-mir-8072 MI0025908 412 hsa-mir-296 MI0000747 413 hsa-mir-204MI0000284 414 hsa-mir-4454 MI0016800 415 hsa-mir-6722 MI0022557 416hsa-mir-1290 MI0006352 417 hsa-mir-3622a MI0016013 418 hsa-mir-939MI0005761 419 hsa-mir-675 MI0005416 420 hsa-mir-3131 MI0014151 421hsa-mir-4648 MI0017275 422 hsa-mir-1268b MI0016748 423 hsa-mir-6741MI0022586 424 hsa-mir-6893 MI0022740 425 hsa-mir-3162 MI0014192 426hsa-mir-642b MI0016685 427 hsa-mir-4734 MI0017371 428 hsa-mir-150MI0000479 429 hsa-mir-8089 MI0025925 430 hsa-mir-6805 MI0022650 431hsa-mir-7113 MI0022964 432 hsa-mir-6850 MI0022696 433 hsa-mir-6799MI0022644 434 hsa-mir-6768 MI0022613 435 hsa-mir-92b MI0003560 436hsa-mir-3679 MI0016080 437 hsa-mir-4792 MI0017439 438 hsa-mir-3656MI0016056 439 hsa-mir-92a-2 MI0000094 440 hsa-mir-4466 MI0016817 441hsa-mir-4513 MI0016879 442 hsa-mir-6781 MI0022626 443 hsa-mir-4649MI0017276 444 hsa-mir-6775 MI0022620 445 hsa-mir-4651 MI0017279 446hsa-mir-3195 MI0014240 447 hsa-mir-6726 MI0022571 448 hsa-mir-6872MI0022719 449 hsa-mir-371a MI0000779 450 hsa-mir-6777 MI0022622 451hsa-mir-6789 MI0022634 452 hsa-mir-7975 MI0025751 453 hsa-mir-6821MI0022666 454 hsa-mir-4534 MI0016901 455 hsa-mir-619 MI0003633 456hsa-mir-7107 MI0022958 457 hsa-mir-1228 MI0006318 458 hsa-mir-6774MI0022619 459 hsa-mir-6805 MI0022650 460 hsa-mir-23a MI0000079 461hsa-mir-4665 MI0017295 462 hsa-mir-4505 MI0016868 463 hsa-mir-4638MI0017265 464 hsa-mir-24-1 MI0000080 465 hsa-mir-24-2 MI0000081 466hsa-mir-3135b MI0016809 467 hsa-mir-4745 MI0017384 468 hsa-mir-128-1MI0000447 469 hsa-mir-4476 MI0016828 470 hsa-mir-4687 MI0017319 471hsa-mir-3665 MI0016066 472 hsa-mir-6806 MI0022651 473 hsa-mir-3937MI0016593 474 hsa-mir-711 MI0012488 475 hsa-mir-3141 MI0014165 476hsa-mir-3188 MI0014232 477 hsa-mir-4281 MI0015885 478 hsa-mir-5196MI0018175 479 hsa-mir-6880 MI0022727 480 hsa-mir-3960 MI0016964 481hsa-mir-3648-1 MI0016048 482 hsa-mir-3648-2 MI0031512 483 hsa-mir-6721MI0022556 484 hsa-mir-4492 MI0016854 485 hsa-mir-744 MI0005559 486hsa-mir-7704 MI0025240 487 hsa-mir-4749 MI0017388 488 hsa-mir-6794MI0022639 489 hsa-mir-6511a-1 MI0022223 490 hsa-mir-6511a-2 MI0023564491 hsa-mir-6511a-3 MI0023565 492 hsa-mir-6511a-4 MI0023566 493hsa-mir-6824 MI0022669 494 hsa-mir-762 MI0003892 495 hsa-mir-6836MI0022682 496 hsa-mir-6727 MI0022572 497 hsa-mir-4739 MI0017377 498hsa-mir-7977 MI0025753 499 hsa-mir-4484 MI0016845 500 hsa-mir-6515MI0022227 501 hsa-mir-373 MI0000781 502 hsa-mir-4258 MI0015857 503hsa-mir-4674 MI0017305 504 hsa-mir-3180-4 MI0016408 505 hsa-mir-3180-5MI0016409 506 hsa-mir-6076 MI0020353 507 hsa-mir-1238 MI0006328 508hsa-mir-4463 MI0016811 509 hsa-mir-4486 MI0016847 510 hsa-mir-4730MI0017367 511 hsa-mir-6766 MI0022611 512 hsa-mir-4286 MI0015894 513hsa-mir-6511a-1 MI0022223 514 hsa-mir-6511a-2 MI0023564 515hsa-mir-6511a-3 MI0023565 516 hsa-mir-6511a-4 MI0023566 517 hsa-mir-4739MI0017377 518 hsa-mir-6749 MI0022594 519 isomiR example 1 of SEQ ID NO:2 — 520 isomiR example 2 of SEQ ID NO: 2 — 521 isomiR example 1 of SEQID NO: 3 — 522 isomiR example 2 of SEQ ID NO: 3 — 523 isomiR example 1of SEQ ID NO: 6 — 524 isomiR example 2 of SEQ ID NO: 6 — 525 isomiRexample 1 of SEQ ID NO: 7 — 526 isomiR example 2 of SEQ ID NO: 7 — 527isomiR example 1 of SEQ ID NO: 8 — 528 isomiR example 2 of SEQ ID NO: 8— 529 isomiR example 1 of SEQ ID NO: 11 — 530 isomiR example 2 of SEQ IDNO: 11 — 531 isomiR example 1 of SEQ ID NO: 12 — 532 isomiR example 2 ofSEQ ID NO: 12 — 533 isomiR example 1 of SEQ ID NO: 13 — 534 isomiRexample 2 of SEQ ID NO: 13 — 535 isomiR example 1 of SEQ ID NO: 15 — 536isomiR example 2 of SEQ ID NO: 15 — 537 isomiR example 1 of SEQ ID NO:19 — 538 isomiR example 2 of SEQ ID NO: 19 — 539 isomiR example 1 of SEQID NO: 20 — 540 isomiR example 2 of SEQ ID NO: 20 — 541 isomiR example 1of SEQ ID NO: 25 — 542 isomiR example 2 of SEQ ID NO: 25 — 543 isomiRexample 1 of SEQ ID NO: 26 — 544 isomiR example 2 of SEQ ID NO: 26 — 545isomiR example 1 of SEQ ID NO: 27 — 546 isomiR example 2 of SEQ ID NO:27 — 547 isomiR example 1 of SEQ ID NO: 29 — 548 isomiR example 2 of SEQID NO: 29 — 549 isomiR example 1 of SEQ ID NO: 31 — 550 isomiR example 2of SEQ ID NO: 31 — 551 isomiR example 1 of SEQ ID NO: 32 — 552 isomiRexample 2 of SEQ ID NO: 32 — 553 isomiR example 1 of SEQ ID NO: 37 — 554isomiR example 2 of SEQ ID NO: 37 — 555 isomiR example 1 of SEQ ID NO:44 — 556 isomiR example 2 of SEQ ID NO: 44 — 557 isomiR example 1 of SEQID NO: 45 — 558 isomiR example 2 of SEQ ID NO: 45 — 559 isomiR example 1of SEQ ID NO: 46 — 560 isomiR example 2 of SEQ ID NO: 46 — 561 isomiRexample 1 of SEQ ID NO: 47 — 562 isomiR example 2 of SEQ ID NO: 47 — 563isomiR example 1 of SEQ ID NO: 48 — 564 isomiR example 2 of SEQ ID NO:48 — 565 isomiR example 1 of SEQ ID NO: 49 — 566 isomiR example 2 of SEQID NO: 49 — 567 isomiR example 1 of SEQ ID NO: 51 — 568 isomiR example 2of SEQ ID NO: 51 — 569 isomiR example 1 of SEQ ID NO: 52 — 570 isomiRexample 2 of SEQ ID NO: 52 — 571 isomiR example 1 of SEQ ID NO: 53 — 572isomiR example 2 of SEQ ID NO: 53 — 573 isomiR example 1 of SEQ ID NO:54 — 574 isomiR example 2 of SEQ ID NO: 54 — 575 isomiR example 1 of SEQID NO: 55 — 576 isomiR example 2 of SEQ ID NO: 55 — 577 isomiR example 1of SEQ ID NO: 56 — 578 isomiR example 2 of SEQ ID NO: 56 — 579 isomiRexample 1 of SEQ ID NO: 57 — 580 isomiR example 2 of SEQ ID NO: 57 — 581isomiR example 1 of SEQ ID NO: 59 — 582 isomiR example 2 of SEQ ID NO:59 — 583 isomiR example 1 of SEQ ID NO: 60 — 584 isomiR example 2 of SEQID NO: 60 — 585 isomiR example 1 of SEQ ID NO: 61 — 586 isomiR example 2of SEQ ID NO: 61 — 587 isomiR example 1 of SEQ ID NO: 62 — 588 isomiRexample 2 of SEQ ID NO: 62 — 589 isomiR example 1 of SEQ ID NO: 63 — 590isomiR example 2 of SEQ ID NO: 63 — 591 isomiR example 1 of SEQ ID NO:71 — 592 isomiR example 2 of SEQ ID NO: 71 — 593 isomiR example 1 of SEQID NO: 72 — 594 isomiR example 2 of SEQ ID NO: 72 — 595 isomiR example 1of SEQ ID NO: 73 — 596 isomiR example 2 of SEQ ID NO: 73 — 597 isomiRexample 1 of SEQ ID NO: 74 — 598 isomiR example 2 of SEQ ID NO: 74 — 599isomiR example 1 of SEQ ID NO: 76 — 600 isomiR example 2 of SEQ ID NO:76 — 601 isomiR example 1 of SEQ ID NO: 77 — 602 isomiR example 2 of SEQID NO: 77 — 603 isomiR example 1 of SEQ ID NO: 78 — 604 isomiR example 2of SEQ ID NO: 78 — 605 isomiR example 1 of SEQ ID NO: 79 — 606 isomiRexample 2 of SEQ ID NO: 79 — 607 isomiR example 1 of SEQ ID NO: 83 — 608isomiR example 2 of SEQ ID NO: 83 — 609 isomiR example 1 of SEQ ID NO:84 — 610 isomiR example 2 of SEQ ID NO: 84 — 611 isomiR example 1 of SEQID NO: 86 — 612 isomiR example 2 of SEQ ID NO: 86 — 613 isomiR example 1of SEQ ID NO: 87 — 614 isomiR example 2 of SEQ ID NO: 87 — 615 isomiRexample 1 of SEQ ID NO: 88 — 616 isomiR example 2 of SEQ ID NO: 88 — 617isomiR example 1 of SEQ ID NO: 89 — 618 isomiR example 2 of SEQ ID NO:89 — 619 isomiR example 1 of SEQ ID NO: 90 — 620 isomiR example 2 of SEQID NO: 90 — 621 isomiR example 1 of SEQ ID NO: 92 — 622 isomiR example 2of SEQ ID NO: 92 — 623 isomiR example 1 of SEQ ID NO: 94 — 624 isomiRexample 2 of SEQ ID NO: 94 — 625 isomiR example 1 of SEQ ID NO: 98 — 626isomiR example 2 of SEQ ID NO: 98 — 627 isomiR example 1 of SEQ ID NO:102 — 628 isomiR example 2 of SEQ ID NO: 102 — 629 isomiR example 1 ofSEQ ID NO: 105 — 630 isomiR example 2 of SEQ ID NO: 105 — 631 isomiRexample 1 of SEQ ID NO: 106 — 632 isomiR example 2 of SEQ ID NO: 106 —633 isomiR example 1 of SEQ ID NO: 108 — 634 isomiR example 2 of SEQ IDNO: 108 — 635 isomiR example 1 of SEQ ID NO: 111 — 636 isomiR example 2of SEQ ID NO: 111 — 637 isomiR example 1 of SEQ ID NO: 112 — 638 isomiRexample 2 of SEQ ID NO: 112 — 639 isomiR example 1 of SEQ ID NO: 113 —640 isomiR example 2 of SEQ ID NO: 113 — 641 isomiR example 1 of SEQ IDNO: 114 — 642 isomiR example 2 of SEQ ID NO: 114 — 643 isomiR example 1of SEQ ID NO: 116 — 644 isomiR example 2 of SEQ ID NO: 116 — 645 isomiRexample 1 of SEQ ID NO: 117 — 646 isomiR example 2 of SEQ ID NO: 117 —647 isomiR example 1 of SEQ ID NO: 118 — 648 isomiR example 2 of SEQ IDNO: 118 — 649 isomiR example 1 of SEQ ID NO: 122 — 650 isomiR example 2of SEQ ID NO: 122 — 651 isomiR example 1 of SEQ ID NO: 123 — 652 isomiRexample 2 of SEQ ID NO: 123 — 653 isomiR example 1 of SEQ ID NO: 124 —654 isomiR example 2 of SEQ ID NO: 124 — 655 isomiR example 1 of SEQ IDNO: 128 — 656 isomiR example 2 of SEQ ID NO: 128 — 657 isomiR example 1of SEQ ID NO: 129 — 658 isomiR example 2 of SEQ ID NO: 129 — 659 isomiRexample 1 of SEQ ID NO: 133 — 660 isomiR example 2 of SEQ ID NO: 133 —661 isomiR example 1 of SEQ ID NO: 134 — 662 isomiR example 2 of SEQ IDNO: 134 — 663 isomiR example 1 of SEQ ID NO: 135 — 664 isomiR example 2of SEQ ID NO: 135 — 665 isomiR example 1 of SEQ ID NO: 136 — 666 isomiRexample 2 of SEQ ID NO: 136 — 667 isomiR example 1 of SEQ ID NO: 137 —668 isomiR example 2 of SEQ ID NO: 137 — 669 isomiR example 1 of SEQ IDNO: 140 — 670 isomiR example 2 of SEQ ID NO: 140 — 671 isomiR example 1of SEQ ID NO: 141 — 672 isomiR example 2 of SEQ ID NO: 141 — 673 isomiRexample 1 of SEQ ID NO: 145 — 674 isomiR example 2 of SEQ ID NO: 145 —675 isomiR example 1 of SEQ ID NO: 146 — 676 isomiR example 2 of SEQ IDNO: 146 — 677 isomiR example 1 of SEQ ID NO: 147 — 678 isomiR example 2of SEQ ID NO: 147 — 679 isomiR example 1 of SEQ ID NO: 148 — 680 isomiRexample 2 of SEQ ID NO: 148 — 681 isomiR example 1 of SEQ ID NO: 149 —682 isomiR example 2 of SEQ ID NO: 149 — 683 isomiR example 1 of SEQ IDNO: 150 — 684 isomiR example 2 of SEQ ID NO: 150 — 685 isomiR example 1of SEQ ID NO: 151 — 686 isomiR example 2 of SEQ ID NO: 151 — 687 isomiRexample 1 of SEQ ID NO: 153 — 688 isomiR example 2 of SEQ ID NO: 153 —689 isomiR example 1 of SEQ ID NO: 154 — 690 isomiR example 2 of SEQ IDNO: 154 — 691 isomiR example 1 of SEQ ID NO: 155 — 692 isomiR example 2of SEQ ID NO: 155 — 693 isomiR example 1 of SEQ ID NO: 157 — 694 isomiRexample 2 of SEQ ID NO: 157 — 695 isomiR example 1 of SEQ ID NO: 158 —696 isomiR example 2 of SEQ ID NO: 158 — 697 isomiR example 1 of SEQ IDNO: 159 — 698 isomiR example 2 of SEQ ID NO: 159 — 699 isomiR example 1of SEQ ID NO: 160 — 700 isomiR example 2 of SEQ ID NO: 160 — 701 isomiRexample 1 of SEQ ID NO: 161 — 702 isomiR example 2 of SEQ ID NO: 161 —703 isomiR example 1 of SEQ ID NO: 162 — 704 isomiR example 2 of SEQ IDNO: 162 — 705 isomiR example 1 of SEQ ID NO: 163 — 706 isomiR example 2of SEQ ID NO: 163 — 707 isomiR example 1 of SEQ ID NO: 166 — 708 isomiRexample 2 of SEQ ID NO: 166 — 709 isomiR example 1 of SEQ ID NO: 167 —710 isomiR example 2 of SEQ ID NO: 167 — 711 isomiR example 1 of SEQ IDNO: 168 — 712 isomiR example 2 of SEQ ID NO: 168 — 713 isomiR example 1of SEQ ID NO: 169 — 714 isomiR example 2 of SEQ ID NO: 169 — 715 isomiRexample 1 of SEQ ID NO: 176 — 716 isomiR example 2 of SEQ ID NO: 176 —717 isomiR example 1 of SEQ ID NO: 177 — 718 isomiR example 2 of SEQ IDNO: 177 — 719 isomiR example 1 of SEQ ID NO: 178 — 720 isomiR example 2of SEQ ID NO: 178 — 721 isomiR example 1 of SEQ ID NO: 179 — 722 isomiRexample 2 of SEQ ID NO: 179 — 723 isomiR example 1 of SEQ ID NO: 180 —724 isomiR example 2 of SEQ ID NO: 180 — 725 isomiR example 1 of SEQ IDNO: 181 — 726 isomiR example 2 of SEQ ID NO: 181 — 727 isomiR example 1of SEQ ID NO: 182 — 728 isomiR example 2 of SEQ ID NO: 182 — 729 isomiRexample 1 of SEQ ID NO: 184 — 730 isomiR example 2 of SEQ ID NO: 184 —731 isomiR example 1 of SEQ ID NO: 186 — 732 isomiR example 2 of SEQ IDNO: 186 — 733 isomiR example 1 of SEQ ID NO: 187 — 734 isomiR example 2of SEQ ID NO: 187 — 735 isomiR example 1 of SEQ ID NO: 190 — 736 isomiRexample 2 of SEQ ID NO: 190 — 737 isomiR example 1 of SEQ ID NO: 193 —738 isomiR example 2 of SEQ ID NO: 193 — 739 isomiR example 1 of SEQ IDNO: 196 — 740 isomiR example 2 of SEQ ID NO: 196 — 741 isomiR example 1of SEQ ID NO: 198 — 742 isomiR example 2 of SEQ ID NO: 198 — 743 isomiRexample 1 of SEQ ID NO: 201 — 744 isomiR example 2 of SEQ ID NO: 201 —745 isomiR example 1 of SEQ ID NO: 202 — 746 isomiR example 2 of SEQ IDNO: 202 — 747 isomiR example 1 of SEQ ID NO: 203 — 748 isomiR example 2of SEQ ID NO: 203 — 749 isomiR example 1 of SEQ ID NO: 204 — 750 isomiRexample 2 of SEQ ID NO: 204 — 751 isomiR example 1 of SEQ ID NO: 205 —752 isomiR example 2 of SEQ ID NO: 205 — 753 isomiR example 1 of SEQ IDNO: 206 — 754 isomiR example 2 of SEQ ID NO: 206 — 755 isomiR example 1of SEQ ID NO: 207 — 756 isomiR example 2 of SEQ ID NO: 207 — 757 isomiRexample 1 of SEQ ID NO: 208 — 758 isomiR example 2 of SEQ ID NO: 208 —759 isomiR example 1 of SEQ ID NO: 209 — 760 isomiR example 2 of SEQ IDNO: 209 — 761 isomiR example 1 of SEQ ID NO: 210 — 762 isomiR example 2of SEQ ID NO: 210 — 763 isomiR example 1 of SEQ ID NO: 211 — 764 isomiRexample 2 of SEQ ID NO: 211 — 765 isomiR example 1 of SEQ ID NO: 214 —766 isomiR example 2 of SEQ ID NO: 214 — 767 isomiR example 1 of SEQ IDNO: 215 — 768 isomiR example 2 of SEQ ID NO: 215 — 769 isomiR example 1of SEQ ID NO: 216 — 770 isomiR example 2 of SEQ ID NO: 216 — 771 isomiRexample 1 of SEQ ID NO: 217 — 772 isomiR example 2 of SEQ ID NO: 217 —773 isomiR example 1 of SEQ ID NO: 218 — 774 isomiR example 2 of SEQ IDNO: 218 — 775 isomiR example 1 of SEQ ID NO: 220 — 776 isomiR example 2of SEQ ID NO: 220 — 777 isomiR example 1 of SEQ ID NO: 221 — 778 isomiRexample 2 of SEQ ID NO: 221 — 779 isomiR example 1 of SEQ ID NO: 222 —780 isomiR example 2 of SEQ ID NO: 222 — 781 isomiR example 1 of SEQ IDNO: 223 — 782 isomiR example 2 of SEQ ID NO: 223 — 783 isomiR example 1of SEQ ID NO: 224 — 784 isomiR example 2 of SEQ ID NO: 224 — 785 isomiRexample 1 of SEQ ID NO: 226 — 786 isomiR example 2 of SEQ ID NO: 226 —787 isomiR example 1 of SEQ ID NO: 228 — 788 isomiR example 2 of SEQ IDNO: 228 — 789 isomiR example 1 of SEQ ID NO: 233 — 790 isomiR example 2of SEQ ID NO: 233 — 791 isomiR example 1 of SEQ ID NO: 235 — 792 isomiRexample 2 of SEQ ID NO: 235 — 793 isomiR example 1 of SEQ ID NO: 236 —794 isomiR example 2 of SEQ ID NO: 236 — 795 isomiR example 1 of SEQ IDNO: 237 — 796 isomiR example 2 of SEQ ID NO: 237 — 797 isomiR example 1of SEQ ID NO: 239 — 798 isomiR example 2 of SEQ ID NO: 239 — 799 isomiRexample 1 of SEQ ID NO: 240 — 800 isomiR example 2 of SEQ ID NO: 240 —801 isomiR example 1 of SEQ ID NO: 243 — 802 isomiR example 2 of SEQ IDNO: 243 — 803 isomiR example 1 of SEQ ID NO: 244 — 804 isomiR example 2of SEQ ID NO: 244 — 805 isomiR example 1 of SEQ ID NO: 245 — 806 isomiRexample 2 of SEQ ID NO: 245 — 807 isomiR example 1 of SEQ ID NO: 247 —808 isomiR example 2 of SEQ ID NO: 247 — 809 isomiR example 1 of SEQ IDNO: 248 — 810 isomiR example 2 of SEQ ID NO: 248 — 811 isomiR example 1of SEQ ID NO: 249 — 812 isomiR example 2 of SEQ ID NO: 249 — 813hsa-miR-145-5p MIMAT0000437 814 hsa-let-7f-5p MIMAT0000067 815hsa-miR-146a-5p MIMAT0000449 816 hsa-let-7d-5p MIMAT0000065 817hsa-let-7a-5p MIMAT0000062

The present specification incorporates the contents disclosed inJapanese Patent Application No. 2016-073132 (filing date: Mar. 31, 2016)to which the present application claims priorities.

Advantageous Effect of Invention

According to the present invention, early pancreatic cancer orpancreatic cancer precursor lesion can be detected easily and in highaccuracy.

For example, the presence or absence of early pancreatic cancer or apancreatic cancer precursor lesion in patients can be easily detected byusing, as indicators, the determined expression levels of several miRNAsin blood, serum, and/or plasma of the patients, which can be collectedwith minimal invasiveness.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 This figure shows the relationship between the nucleotidesequences of hsa-miR-1343-3p represented by SEQ ID NO: 118 andhsa-miR-1343-5p represented by SEQ ID NO: 14, which are produced fromhsa-mir-1343 represented by SEQ ID NO: 264 as a precursor.

FIG. 2 In the left diagram of FIG. 2, a discriminant(3.10×hsa-miR-miR-6784-5p−39.85) was prepared by use of Fisher'sdiscriminant analysis from the expression level measurement values ofhsa-miR-6784-5p (SEQ ID NO: 1) in pancreatic cancer precursor lesionpatients (21 persons), early pancreatic cancer patients (31 persons),and healthy subjects (123 persons) selected as a training cohort, anddiscriminant scores obtained with the discriminant are plotted on thevertical axis with the cohort plotted on the horizontal axis. The dottedline in the diagram depicts a discriminant boundary on which thediscriminant score is 0 and by which the two groups are discriminated.In the right diagram of FIG. 2, the vertical axis plots discriminantscores for the expression level measurement values of hsa-miR-6784-5p(SEQ ID NO: 1) in pancreatic cancer precursor lesion patients (12persons), early pancreatic cancer patients (13 persons), and healthysubjects (61 persons) selected as a validation cohort, wherein thediscriminant scores are obtained with the discriminant prepared from thetraining cohort, and the horizontal axis plots the cohort. The dottedline in the diagram depicts the discriminant boundary on which thediscriminant score is 0 and by which the two groups are discriminated.

FIG. 3 In the left diagram of FIG. 3, a discriminant(1.90×hsa-miR-6784-5p+1.72×hsa-miR-1181−34.50) was prepared by use ofFisher's discriminant analysis from the expression level measurementvalues of hsa-miR-6784-5p (SEQ ID NO: 1) and hsa-miR-1181 (SEQ ID NO: 2)in pancreatic cancer precursor lesion patients (21 persons), earlypancreatic cancer patients (31 persons), and healthy subjects (123persons) selected as a training cohort, and discriminant scores obtainedwith the discriminant are plotted on the vertical axis with the cohortplotted on the horizontal axis. The dotted line in the diagram depicts adiscriminant boundary on which the discriminant score is 0 and by whichthe two groups are discriminated. In the right diagram of FIG. 3, thevertical axis plots discriminant scores for the expression levelmeasurement values of hsa-miR-6784-5p (SEQ ID NO: 1) and hsa-miR-1181(SEQ ID NO: 2) in pancreatic cancer precursor lesion patients (12persons), early pancreatic cancer patients (13 persons), and healthysubjects (61 persons) selected as a validation cohort, wherein thediscriminant scores are obtained with the discriminant prepared from thetraining cohort, and the horizontal axis plots the cohort. The dottedline in the diagram depicts a discriminant boundary on which thediscriminant score is 0 and by which the two groups are discriminated.

FIG. 4 In the top diagram of FIG. 4, a discriminant(0.48×hsa-miR-4695-5p−1.75×hsa-miR-5090+1.31×hsa-miR-4673-0.98×hsa-miR-6813-5p−1.16×hsa-miR-642a-3p+15.39)was prepared by use of Fisher's discriminant analysis from theexpression level measurement values of hsa-miR-4695-5p (SEQ ID NO: 106),hsa-miR-5090 (SEQ ID NO: 12), hsa-miR-4673 (SEQ ID NO: 137),hsa-miR-6813-5p (SEQ ID NO: 119), and hsa-miR-642a-3p (SEQ ID NO: 105)in 21 pancreatic cancer precursor lesion patients, 31 early pancreaticcancer patients, 128 healthy subjects, 61 advanced pancreatic cancerpatients, 66 bile duct cancer patients, 51 breast cancer patients, 35prostate cancer patients, 31 colorectal cancer patients, 32 stomachcancer patients, 34 esophageal cancer patients, 38 liver cancerpatients, 15 benign pancreatic disease patients, and 26 benign prostaticdisease patients selected as a training cohort, and discriminant scoresobtained with the discriminant are plotted on the vertical axis with thecohort plotted on the horizontal axis. The dotted line in the diagramdepicts a discriminant boundary on which the discriminant score is 0 andby which the two groups are discriminated. In the bottom diagram of FIG.4, the vertical axis plots discriminant scores for the expression levelmeasurement values of hsa-miR-4695-5p (SEQ ID NO: 106), hsa-miR-5090(SEQ ID NO: 12), hsa-miR-4673 (SEQ ID NO: 137), hsa-miR-6813-5p (SEQ IDNO: 119), and hsa-miR-642a-3p (SEQ ID NO: 105) in 12 pancreatic cancerprecursor lesion patients, 13 early pancreatic cancer patients, 56healthy subjects, 39 advanced pancreatic cancer patients, 32 bile ductcancer patients, 23 breast cancer patients, 17 prostate cancer patients,19 colorectal cancer patients, 18 stomach cancer patients, 16 esophagealcancer patients, 14 liver cancer patients, and 24 benign pancreatic andprostatic disease patients selected as a validation cohort, wherein thediscriminant scores are obtained with the discriminant prepared from thetraining cohort, and the horizontal axis plots the cohort. The dottedline in the diagram depicts a discriminant boundary on which thediscriminant score is 0 and by which the two groups are discriminated.

MODES FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be further described in detail.

1. Target Nucleic Acid for Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion

Primary target nucleic acids, as early pancreatic cancer or pancreaticcancer precursor lesion markers, for detecting the presence and/orabsence of early pancreatic cancer or a pancreatic cancer precursorlesion or early pancreatic cancer or pancreatic cancer precursor lesioncells using the nucleic acid probes or the primers for the detection ofearly pancreatic cancer or a pancreatic cancer precursor lesion definedabove according to the present invention comprise at least one miRNAselected from the group consisting of the following miRNAs:hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p,hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p,hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090,hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p,hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p,hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p,hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p,hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087,hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p,hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p,hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p,hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p,hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688,hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126,hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498,hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p,hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p,hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p,hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448,hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p,hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p,hsa-miR-6824-5p, hsa-miR-6766-3p, hsa-miR-6511a-5p, and hsa-miR-6749-5p.

Furthermore, at least one miRNAs selected from the group consisting ofthe following other early pancreatic cancer or pancreatic cancerprecursor lesion markers that can be combined with these miRNAs, i.e.,hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638,hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p,hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p,hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p,hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p,hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197,hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185,hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p,hsa-miR-4787-5p, hsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p,hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294,hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718,hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741,hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673,hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a,hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p,hsa-miR-4417, hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p,hsa-miR-5585-3p, hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p,hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290,hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131,hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p,hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p,hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p,hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p,hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466,hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p,hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p,hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975,hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p,hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p,hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p,hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476,hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937,hsa-miR-711, hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p,hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p,hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p,hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739,hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p,hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p,hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-4286, and hsa-miR-4739can also be preferably used as target nucleic acids.

These miRNAs include, for example, a human gene comprising a nucleotidesequence represented by any of SEQ ID NOs: 1 to 250 (i.e.,hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p,hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p,hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090,hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p,hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p,hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p,hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p,hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087,hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p,hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p,hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p,hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p,hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688,hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126,hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498,hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p,hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p,hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p,hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448,hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p,hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-1908-5p, hsa-miR-6729-5p,hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196,hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689,hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p,hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508,hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p,hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641,hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p,hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p,hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488,hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231,hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p,hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467,hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p,hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p,hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417,hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p,hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p,hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p,hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648,hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p,hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089,hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p,hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792,hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513,hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651,hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p,hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p,hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p,hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p,hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b,hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p,hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141,hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p,hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492,hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-6794-5p,hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-762, hsa-miR-6836-3p,hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484,hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674,hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486,hsa-miR-4730, hsa-miR-6766-3p, hsa-miR-4286, hsa-miR-6511a-5p,hsa-miR-4739, and hsa-miR-6749-5p, respectively), a congener, atranscript thereof, or/and a variant or a derivative thereof. In thiscontext, the gene, the congener, the transcript, the variant, and thederivative are as defined above.

The target nucleic acid is preferably a human gene comprising anucleotide sequence represented by any of SEQ ID NOs: 1 to 812 or atranscript thereof, more preferably the transcript, i.e., a miRNA or itsprecursor RNA (pri-miRNA or pre-miRNA).

The first target gene is the hsa-miR-6784-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The second target gene is the hsa-miR-1181 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The third target gene is the hsa-miR-671-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The fourth target gene is the hsa-miR-6857-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The fifth target gene is the hsa-miR-4276 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The sixth target gene is the hsa-miR-1914-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The seventh target gene is the hsa-miR-149-3p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The eighth target gene is the hsa-miR-937-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The ninth target gene is the hsa-miR-4675 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 10th target gene is the hsa-miR-6795-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 11th target gene is the hsa-miR-4731-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 12th target gene is the hsa-miR-5090 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 13th target gene is the hsa-miR-3620-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 14th target gene is the hsa-miR-1343-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 15th target gene is the hsa-miR-6717-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 16th target gene is the hsa-miR-6825-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 17th target gene is the hsa-miR-6738-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 18th target gene is the hsa-miR-6769a-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 19th target gene is the hsa-miR-4728-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 20th target gene is the hsa-miR-652-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 21st target gene is the hsa-miR-4257 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 22nd target gene is the hsa-miR-6785-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 23rd target gene is the hsa-miR-7110-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 24th target gene is the hsa-miR-6887-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 25th target gene is the hsa-miR-887-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 26th target gene is the hsa-miR-1228-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 27th target gene is the hsa-miR-5572 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 28th target gene is the hsa-miR-6782-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 29th target gene is the hsa-miR-4298 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 30th target gene is the hsa-miR-6786-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 31st target gene is the hsa-miR-5010-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 32nd target gene is the hsa-miR-6087 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 33rd target gene is the hsa-miR-6765-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 34th target gene is the hsa-miR-6732-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 35th target gene is the hsa-miR-6787-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 36th target gene is the hsa-miR-6737-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 37th target gene is the hsa-miR-128-2-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 38th target gene is the hsa-miR-4270 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 39th target gene is the hsa-miR-6861-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 40th target gene is the hsa-miR-6756-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 41st target gene is the hsa-miR-1229-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 42nd target gene is the hsa-miR-6891-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 43rd target gene is the hsa-miR-6848-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 44th target gene is the hsa-miR-1237-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 45th target gene is the hsa-miR-30c-1-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 46th target gene is the hsa-miR-1233-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 47th target gene is the hsa-miR-211-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 48th target gene is the hsa-miR-4758-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 49th target gene is the hsa-miR-614 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 50th target gene is the hsa-miR-6746-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 51st target gene is the hsa-miR-1915-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 52nd target gene is the hsa-miR-4688 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 53rd target gene is the hsa-miR-3917 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 54th target gene is the hsa-miR-5787 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 55th target gene is the hsa-miR-4632-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 56th target gene is the hsa-miR-6126 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 57th target gene is the hsa-miR-135a-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 58th target gene is the hsa-miR-8063 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 59th target gene is the hsa-miR-5698 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 60th target gene is the hsa-miR-6089 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 61st target gene is the hsa-miR-498 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 62nd target gene is the hsa-miR-296-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 63rd target gene is the hsa-miR-4419b gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 64th target gene is the hsa-miR-6802-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 65th target gene is the hsa-miR-6829-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 66th target gene is the hsa-miR-6803-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 67th target gene is the hsa-miR-1199-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 68th target gene is the hsa-miR-6840-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 69th target gene is the hsa-miR-6752-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 70th target gene is the hsa-miR-6798-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 71st target gene is the hsa-miR-6131 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 72nd target gene is the hsa-miR-4667-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 73rd target gene is the hsa-miR-6510-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 74th target gene is the hsa-miR-4690-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 75th target gene is the hsa-miR-920 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 76th target gene is the hsa-miR-23b-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 77th target gene is the hsa-miR-4448 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 78th target gene is the hsa-miR-2110 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 79th target gene is the hsa-miR-4706 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 80th target gene is the hsa-miR-7845-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 81st target gene is the hsa-miR-6808-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 82nd target gene is the hsa-miR-4447 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 83rd target gene is the hsa-miR-6869-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known reports show that change in the expression of the geneor the transcript thereof can serve as a marker for early pancreaticcancer or a pancreatic cancer precursor lesion.

The 84th target gene is the hsa-miR-1908-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 85th target gene is the hsa-miR-6729-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 86th target gene is the hsa-miR-5195-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 87th target gene is the hsa-miR-638 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 88th target gene is the hsa-miR-6125 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 89th target gene is the hsa-miR-3178 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 90th target gene is the hsa-miR-3196 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 91st target gene is the hsa-miR-8069 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 92nd target gene is the hsa-miR-4723-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 93rd target gene is the hsa-miR-4746-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 94th target gene is the hsa-miR-4689 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 95th target gene is the hsa-miR-6816-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 96th target gene is the hsa-miR-6757-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 97th target gene is the hsa-miR-7109-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 98th target gene is the hsa-miR-6724-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 99th target gene is the hsa-miR-1225-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 100th target gene is the hsa-miR-6875-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 101st target gene is the hsa-miR-7108-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 102nd target gene is the hsa-miR-4508 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 103rd target gene is the hsa-miR-6085 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 104th target gene is the hsa-miR-6779-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 105th target gene is the hsa-miR-642a-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 106th target gene is the hsa-miR-4695-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 107th target gene is the hsa-miR-7847-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 108th target gene is the hsa-miR-3197 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 109th target gene is the hsa-miR-6769b-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. Thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer(Patent Literature 2 described above).

The 110th target gene is the hsa-miR-7641 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 111th target gene is the hsa-miR-187-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 112th target gene is the hsa-miR-3185 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 113th target gene is the hsa-miR-2861 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 114th target gene is the hsa-miR-3940-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 115th target gene is the hsa-miR-1203 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 116th target gene is the hsa-miR-615-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 117th target gene is the hsa-miR-4787-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 118th target gene is the hsa-miR-1343-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 119th target gene is the hsa-miR-6813-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 120th target gene is the hsa-miR-1225-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 121 st target gene is the hsa-miR-602 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 122nd target gene is the hsa-miR-4488 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 123rd target gene is the hsa-miR-125a-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 124th target gene is the hsa-miR-5100 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 125th target gene is the hsa-miR-4294 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 126th target gene is the hsa-miR-1231 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 127th target gene is the hsa-miR-6765-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 128th target gene is the hsa-miR-4442 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 129th target gene is the hsa-miR-718 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 130th target gene is the hsa-miR-6780b-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. Thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer(Patent Literature 2 described above).

The 131st target gene is the hsa-miR-6090 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 132nd target gene is the hsa-miR-6845-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 133rd target gene is the hsa-miR-4741 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 134th target gene is the hsa-miR-4467 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 135th target gene is the hsa-miR-4707-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 136th target gene is the hsa-miR-4271 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 137th target gene is the hsa-miR-4673 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 138th target gene is the hsa-miR-3184-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 139th target gene is the hsa-miR-1469 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 140th target gene is the hsa-miR-4640-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 141st target gene is the hsa-miR-663a gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 142nd target gene is the hsa-miR-6791-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 143rd target gene is the hsa-miR-6826-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 144th target gene is the hsa-miR-4433b-3p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. Thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer(Patent Literature 2 described above).

The 145th target gene is the hsa-miR-1915-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 146th target gene is the hsa-miR-4417 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 147th target gene is the hsa-miR-4449 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 148th target gene is the hsa-miR-4707-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 149th target gene is the hsa-miR-3180-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 150th target gene is the hsa-miR-5585-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 151st target gene is the hsa-miR-1268a gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for early pancreatic cancer ora pancreatic cancer precursor lesion (Patent Literature 4 describedabove).

The 152nd target gene is the hsa-miR-8072 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 153rd target gene is the hsa-miR-296-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for early pancreatic cancer ora pancreatic cancer precursor lesion (Patent Literature 5 describedabove).

The 154th target gene is the hsa-miR-204-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 155th target gene is the hsa-miR-4454 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 156th target gene is the hsa-miR-6722-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 157th target gene is the hsa-miR-1290 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 158th target gene is the hsa-miR-3622a-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. Thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer(Patent Literature 2 described above).

The 159th target gene is the hsa-miR-939-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for early pancreatic cancer ora pancreatic cancer precursor lesion (Patent Literature 4 describedabove).

The 160th target gene is the hsa-miR-675-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 161st target gene is the hsa-miR-3131 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 162nd target gene is the hsa-miR-4648 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 163rd target gene is the hsa-miR-1268b gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 164th target gene is the hsa-miR-6741-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 165th target gene is the hsa-miR-6893-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 166th target gene is the hsa-miR-3162-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 167th target gene is the hsa-miR-642b-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for early pancreatic cancer ora pancreatic cancer precursor lesion (Patent Literature 4 describedabove).

The 168th target gene is the hsa-miR-4734 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 169th target gene is the hsa-miR-150-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 170th target gene is the hsa-miR-8089 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 171st target gene is the hsa-miR-6805-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 172nd target gene is the hsa-miR-7113-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 173rd target gene is the hsa-miR-6850-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 174th target gene is the hsa-miR-6799-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 175th target gene is the hsa-miR-6768-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 176th target gene is the hsa-miR-92b-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 177th target gene is the hsa-miR-3679-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 178th target gene is the hsa-miR-4792 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 179th target gene is the hsa-miR-3656 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 180th target gene is the hsa-miR-92a-2-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. Thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer(Patent Literature 2 described above).

The 181st target gene is the hsa-miR-4466 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 182nd target gene is the hsa-miR-4513 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 183rd target gene is the hsa-miR-6781-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 184th target gene is the hsa-miR-4649-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 185th target gene is the hsa-miR-6775-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 186th target gene is the hsa-miR-4651 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 187th target gene is the hsa-miR-3195 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 188th target gene is the hsa-miR-6726-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 189th target gene is the hsa-miR-6872-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 190th target gene is the hsa-miR-371a-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 191st target gene is the hsa-miR-6777-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 192nd target gene is the hsa-miR-6789-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 193rd target gene is the hsa-miR-7975 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 194th target gene is the hsa-miR-6821-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 195th target gene is the hsa-miR-4534 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 196th target gene is the hsa-miR-619-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 197th target gene is the hsa-miR-7107-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 198th target gene is the hsa-miR-1228-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 199th target gene is the hsa-miR-6774-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 200th target gene is the hsa-miR-6805-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 201st target gene is the hsa-miR-23a-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 3 described above).

The 202nd target gene is the hsa-miR-4665-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 203rd target gene is the hsa-miR-4505 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 204th target gene is the hsa-miR-4638-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 205th target gene is the hsa-miR-24-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 206th target gene is the hsa-miR-3135b gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 207th target gene is the hsa-miR-4745-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 208th target gene is the hsa-miR-128-1-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. Thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer(Patent Literature 2 described above).

The 209th target gene is the hsa-miR-4476 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 210th target gene is the hsa-miR-4687-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 211th target gene is the hsa-miR-3665 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 212th target gene is the hsa-miR-6806-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 213th target gene is the hsa-miR-3937 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 214th target gene is the hsa-miR-711 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 215th target gene is the hsa-miR-3141 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 216th target gene is the hsa-miR-3188 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 217th target gene is the hsa-miR-4281 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 218th target gene is the hsa-miR-5196-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 219th target gene is the hsa-miR-6880-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 220th target gene is the hsa-miR-3960 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 221st target gene is the hsa-miR-3648 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 1 described above).

The 222nd target gene is the hsa-miR-6721-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 223rd target gene is the hsa-miR-4492 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 224th target gene is the hsa-miR-744-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 225th target gene is the hsa-miR-7704 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 226th target gene is the hsa-miR-4749-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 227th target gene is the hsa-miR-6794-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer.

The 228th target gene is the hsa-miR-6511a-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. None of thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer.

The 229th target gene is the hsa-miR-6824-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer.

The 230th target gene is the hsa-miR-762 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 231st target gene is the hsa-miR-6836-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 232nd target gene is the hsa-miR-6727-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 233rd target gene is the hsa-miR-4739 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 234th target gene is the hsa-miR-7977 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 235th target gene is the hsa-miR-4484 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 236th target gene is the hsa-miR-6515-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 237th target gene is the hsa-miR-373-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 238th target gene is the hsa-miR-4258 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 239th target gene is the hsa-miR-4674 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 240th target gene is the hsa-miR-3180 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 241st target gene is the hsa-miR-6076 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 242nd target gene is the hsa-miR-1238-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 243rd target gene is the hsa-miR-4463 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 244th target gene is the hsa-miR-4486 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 245th target gene is the hsa-miR-4730 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 246th target gene is the hsa-miR-6766-3p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer.

The 247th target gene is the hsa-miR-4286 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer (PatentLiterature 2 described above).

The 248th target gene is the hsa-miR-6511a-5p gene, a congener thereof,a transcript thereof, or a variant or a derivative thereof. None of thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer.

The 249th target gene is the hsa-miR-4739 gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. The previouslyknown report shows that change in the expression of the gene or thetranscript thereof can serve as a marker for pancreatic cancer(Non-Patent Literature 5 described above).

The 250th target gene is the hsa-miR-6749-5p gene, a congener thereof, atranscript thereof, or a variant or a derivative thereof. None of thepreviously known report shows that change in the expression of the geneor the transcript thereof can serve as a marker for pancreatic cancer.

2. Nucleic Acid Probe or Primer for Detection of Early Pancreatic Canceror a Pancreatic Cancer Precursor Lesion

In the present invention, a nucleic acid capable of specifically bindingto any of the target nucleic acids as the early pancreatic cancer orpancreatic cancer precursor lesion markers described above can be usedas a nucleic acid, for example, a nucleic acid probe or a primer, forthe detection or diagnosis of early pancreatic cancer or a pancreaticcancer precursor lesion.

In the present invention, the nucleic acid probes or the primers thatcan be used for detecting early pancreatic cancer or a pancreatic cancerprecursor lesion or for diagnosing early pancreatic cancer or apancreatic cancer precursor lesion enable qualitative and/orquantitative measurement of the presence, expression level, or existingamount (abundance) of: any of human-derived hsa-miR-6784-5p,hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p, hsa-miR-4276,hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p, hsa-miR-4675,hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090, hsa-miR-3620-5p,hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p, hsa-miR-6738-5p,hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p, hsa-miR-4257,hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p, hsa-miR-887-3p,hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p, hsa-miR-4298,hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087, hsa-miR-6765-5p,hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p, hsa-miR-128-2-5p,hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p, hsa-miR-1229-5p,hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p, hsa-miR-30c-1-3p,hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p, hsa-miR-614,hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688, hsa-miR-3917,hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126, hsa-miR-135a-3p,hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498, hsa-miR-296-3p,hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p, hsa-miR-6803-5p,hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p, hsa-miR-6798-5p,hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p, hsa-miR-4690-5p,hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448, hsa-miR-2110, hsa-miR-4706,hsa-miR-7845-5p, hsa-miR-6808-5p, hsa-miR-4447, hsa-miR-6869-5p,hsa-miR-6794-5p, hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-6766-3p,hsa-miR-6511a-5p, and hsa-miR-6749-5p, as target nucleic acids for earlypancreatic cancer or a pancreatic cancer precursor lesion, or acombination thereof; and hsa-miR-1908-5p, hsa-miR-6729-5p,hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196,hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689,hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p,hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508,hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p,hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641,hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p,hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p,hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488,hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231,hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p,hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467,hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p,hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p,hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417,hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p,hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p,hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p,hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648,hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p,hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089,hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p,hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792,hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513,hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651,hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p,hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p,hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p,hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p,hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b,hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p,hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141,hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p,hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492,hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-762,hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977,hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258,hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463,hsa-miR-4486, hsa-miR-4730, hsa-miR-4286, and hsa-miR-4739, which can befurther optionally combined therewith or a combination thereof;congeners thereof: transcripts thereof: or variants or derivativesthereof.

The expression levels of the target nucleic acids described above areincreased or decreased (hereinafter, referred to as“increased/decreased”) depending on the identities of the target nucleicacids in subjects having early pancreatic cancer or a pancreatic cancerprecursor lesion as compared with healthy subjects. For example, Table 2illustrates change in the expression levels of target miRNAscorresponding to SEQ ID NOs: 1 to 226 in the blood (serum) of pancreaticcancer precursor lesion patients (humans) relative to healthy subjects.As shown in Table 2, the expression levels of the target miRNAs areincreased or decreased depending on the identities of the target miRNAs.In the present invention, any of the target miRNAs selected this timeand described herein can be used for the detection and determination ofearly pancreatic cancer or a pancreatic cancer precursor lesion in asubject.

Accordingly, the present invention can be effectively used for measuringexpression levels of the target nucleic acids in body fluids fromsubjects (e.g., humans) suspected of having early pancreatic cancer or apancreatic cancer precursor lesion and body fluids from healthy subjectsand thereby detecting early pancreatic cancer or a pancreatic cancerprecursor lesion with high accuracy through the comparison thereof. Thepresent invention can also be effectively used for measuring expressionlevels of the target nucleic acids in body fluids from subjects (e.g.,humans) suspected of having early pancreatic cancer or a pancreaticcancer precursor lesion and body fluids from advanced pancreatic cancerpatients, bile duct cancer patients, breast cancer patients, prostatecancer patients, colorectal cancer patients, stomach cancer patients,esophageal cancer patients, liver cancer patients, benign pancreaticdisease patients, or benign prostatic disease patients, or a combinationthereof and thereby specifically discriminating early pancreatic canceror a pancreatic cancer precursor lesion from other cancers, benigndiseases or the like, with high accuracy through the comparison thereof.

The nucleic acid probe or the primer that can be used in the presentinvention is a nucleic acid probe(s) capable of specifically binding toa polynucleotide(s) consisting of a nucleotide sequence(s) representedby at least one, at least two, at least three, at least four, or atleast five of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, or aprimer(s) for amplifying a polynucleotide(s) consisting of a nucleotidesequence(s) represented by at least one, at least two, at least three,at least four, or at least five of SEQ ID NOs: 1 to 83, 227 to 229, 246,248, and 250.

The nucleic acid probe or the primer that can be used in the presentinvention may further comprise a nucleic acid probe(s) capable ofspecifically binding to a polynucleotide(s) consisting of a nucleotidesequence(s) represented by at least one, at least two, at least three,at least four, or at least five of SEQ ID NOs: 84 to 226, 230 to 245,247, and 249, or a primer(s) for amplifying a polynucleotide(s)consisting of a nucleotide sequence(s) represented by at least one, atleast two, at least three, at least four, or at least five of SEQ IDNOs: 84 to 226, 230 to 245, 247, and 249.

Specifically, these nucleic acid probes or primers comprise acombination of one or more polynucleotides selected from: a group ofpolynucleotides comprising nucleotide sequences represented by any ofSEQ ID NOs: 1 to 250 or nucleotide sequences derived from the nucleotidesequences by the replacement of u with t, and a group of complementarypolynucleotides thereof; a group of polynucleotides respectivelyhybridizing under stringent conditions (mentioned later) to DNAsconsisting of nucleotide sequences complementary to these nucleotidesequences, and a group of complementary polynucleotides thereof; and agroup of polynucleotides comprising 15 or more, preferably 17 or moreconsecutive nucleotides from the nucleotide sequences of thesepolynucleotide groups. In this respect, the target miRNA used in thepresent invention also includes, for example, precursor miRNAs as shownin SEQ ID NOs: 251 to 518 and isomiRNAs as shown in SEQ ID NOs: 519 to812 in Table 1. The isomiRNAs include those having the number ofnucleotides as short as approximately 15, those having the number ofnucleotides as long as approximately 29, those having mutation such assubstitution, and the like. Hence, in the present invention, the nucleicacid probes or the primers also include nucleic acid probes or primersfor enabling measurement of the expression of precursor miRNAs andtarget isomiRNAs. These polynucleotides can be used as nucleic acidprobes and primers for detecting the early pancreatic cancer orpancreatic cancer precursor lesion markers as target nucleic acids.

More specifically, examples of the nucleic acid probes or the primersthat can be used in the present invention include at least one (i.e.,one or more) polynucleotide selected from the group consisting of thefollowing polynucleotides (a) to (e):

(a) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t, a variant thereof, a derivative thereof, or afragment thereof comprising 15 or more consecutive nucleotides;(b) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250;(c) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227to 229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(d) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t; and(e) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (a) to (d).

In addition to at least one (i.e., one or more) polynucleotides selectedfrom any of the polynucleotides (a) to (e), the nucleic acid probes orthe primers that can be used in the present invention may furthercomprise at least one (i.e., one or more) polynucleotides of thefollowing polynucleotides (f) to (j):

(f) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotidesequence derived from the nucleotide sequence by the replacement of uwith t, a variant thereof, a derivative thereof, or a fragment thereofcomprising 15 or more consecutive nucleotides;(g) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249;(h) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 84 to 226,230 to 245, 247, and 249 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(i) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230 to245, 247, and 249 or a nucleotide sequence derived from the nucleotidesequence by the replacement of u with t; and(j) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (f) to (i).

For the above-mentioned polynucleotides, the “fragment thereofcomprising 15 or more consecutive nucleotides” is derived from thenucleotide sequence of each polynucleotide, and can comprise, but is notlimited to, the number of nucleotides in the range of, for example, from15 consecutive nucleotides to less than the total number of nucleotidesof the sequence, from 17 consecutive nucleotides to less than the totalnumber of nucleotides of the sequence, from 19 consecutive nucleotidesto less than the total number of nucleotides of the sequence, or thelike.

These polynucleotides or fragments thereof used in the present inventionmay each be DNA or RNA.

The polynucleotides that can be used in the present invention can beprepared by use of a general technique such as a DNA recombinationtechnique, a PCR method, or a method using an automatic DNA/RNAsynthesizer.

The DNA recombination technique and the PCR method may employ techniquesdescribed in, for example, Ausubel et al., Current Protocols inMolecular Biology, John Willey & Sons, US (1993); and Sambrook et al.,Molecular Cloning—A Laboratory Manual, Cold Spring Harbor LaboratoryPress, US (1989).

The human-derived hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p,hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p,hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p,hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p,hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p,hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p,hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572,hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p,hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p,hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p,hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p,hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p,hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p,hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126,hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498,hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p,hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p,hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p,hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448,hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p,hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-1908-5p, hsa-miR-6729-5p,hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196,hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689,hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p,hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508,hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p,hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641,hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p,hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p,hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488,hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231,hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p,hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467,hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p,hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p,hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417,hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p,hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p,hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p,hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648,hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p,hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089,hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p,hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792,hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513,hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651,hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p,hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p,hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p,hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p,hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b,hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p,hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141,hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p,hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492,hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p, hsa-miR-6794-5p,hsa-miR-6511a-5p, hsa-miR-6824-5p, hsa-miR-762, hsa-miR-6836-3p,hsa-miR-6727-5p, hsa-miR-4739, hsa-miR-7977, hsa-miR-4484,hsa-miR-6515-3p, hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674,hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486,hsa-miR-4730, hsa-miR-6766-3p, hsa-miR-4286, hsa-miR-6511a-5p,hsa-miR-4739, and hsa-miR-6749-5p represented by SEQ ID NOs: 1 to 250are known in the art, and their obtainment methods are also known asmentioned above. Therefore, each polynucleotide that can be used as anucleic acid probe or a primer in the present invention can be preparedby cloning the gene.

Such nucleic acid probes or primers can be chemically synthesized usingan automatic DNA synthesizer. In general, the phosphoramidite method isused in this synthesis, and single-stranded DNA up to approximately 100nucleotides can be automatically synthesized by this method. Theautomatic DNA synthesizer is commercially available from, for example,Polygen GmbH, ABI, or Applied Biosystems, Inc.

Alternatively, the polynucleotides of the present invention can also beprepared by cDNA cloning methods. The cDNA cloning technique may employ,for example, microRNA Cloning Kit Wako.

In this context, the sequences of the nucleic acid probes and theprimers for detecting the polynucleotide consisting of a nucleotidesequence represented by any of SEQ ID NOs: 1 to 250 do not exist asmiRNAs or precursors thereof in the living body or in vivo. For example,the nucleotide sequences represented by SEQ ID NO: 14 and SEQ ID NO: 118are produced from the precursor represented by SEQ ID NO: 264. Thisprecursor has a hairpin-like structure as shown in FIG. 1, and thenucleotide sequences represented by SEQ ID NO: 14 and SEQ ID NO: 118have mismatch sequences with each other. As such, a nucleotide sequencecompletely complementary to the nucleotide sequence represented by SEQID NO: 14 or SEQ ID NO: 118 does not naturally occur in vivo. Therefore,the nucleic acid probes and the primers for detecting the nucleotidesequence represented by any of SEQ ID NOs: 1 to 250 have artificialnucleotide sequences that do not exist in the living body or in vivo.

3. Kit or Device for Detection of Early Pancreatic Cancer or aPancreatic Cancer Precursor Lesion

The present invention also provides a kit or a device for the detectionof early pancreatic cancer or a pancreatic cancer precursor lesion,comprising one or more polynucleotides (which may include a variant, afragment, or a derivative thereof) that can be used as nucleic acidprobes or primers in the present invention for measuring target nucleicacids as early pancreatic cancer or pancreatic cancer precursor lesionmarkers.

The target nucleic acids as early pancreatic cancer or pancreatic cancerprecursor lesion markers according to the present invention are at leastone nucleic acid selected from the following group A:

Group A:

hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p, hsa-miR-6857-5p,hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p, hsa-miR-937-5p,hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p, hsa-miR-5090,hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p, hsa-miR-6825-5p,hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p, hsa-miR-652-5p,hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p, hsa-miR-6887-5p,hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572, hsa-miR-6782-5p,hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p, hsa-miR-6087,hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p, hsa-miR-6737-5p,hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p, hsa-miR-6756-5p,hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p, hsa-miR-1237-5p,hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p, hsa-miR-4758-5p,hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p, hsa-miR-4688,hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126,hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498,hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p,hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p,hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p,hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448,hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p,hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-6794-5p, hsa-miR-6511a-5p,hsa-miR-6824-5p, hsa-miR-6766-3p, hsa-miR-6511a-5p, and hsa-miR-6749-5p.

Additional target nucleic acids that may be optionally used in themeasurement are at least one nucleic acid selected from the followinggroup B:

Group B:

hsa-miR-1908-5p, hsa-miR-6729-5p, hsa-miR-5195-3p, hsa-miR-638,hsa-miR-6125, hsa-miR-3178, hsa-miR-3196, hsa-miR-8069, hsa-miR-4723-5p,hsa-miR-4746-3p, hsa-miR-4689, hsa-miR-6816-5p, hsa-miR-6757-5p,hsa-miR-7109-5p, hsa-miR-6724-5p, hsa-miR-1225-3p, hsa-miR-6875-5p,hsa-miR-7108-5p, hsa-miR-4508, hsa-miR-6085, hsa-miR-6779-5p,hsa-miR-642a-3p, hsa-miR-4695-5p, hsa-miR-7847-3p, hsa-miR-3197,hsa-miR-6769b-5p, hsa-miR-7641, hsa-miR-187-5p, hsa-miR-3185,hsa-miR-2861, hsa-miR-3940-5p, hsa-miR-1203, hsa-miR-615-5p,hsa-miR-4787-5p, hsa-miR-1343-3p, hsa-miR-6813-5p, hsa-miR-1225-5p,hsa-miR-602, hsa-miR-4488, hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294,hsa-miR-1231, hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718,hsa-miR-6780b-5p, hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741,hsa-miR-4467, hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673,hsa-miR-3184-5p, hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a,hsa-miR-6791-5p, hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p,hsa-miR-4417, hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p,hsa-miR-5585-3p, hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p,hsa-miR-204-3p, hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290,hsa-miR-3622a-5p, hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131,hsa-miR-4648, hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p,hsa-miR-3162-5p, hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p,hsa-miR-8089, hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p,hsa-miR-6799-5p, hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p,hsa-miR-4792, hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466,hsa-miR-4513, hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p,hsa-miR-4651, hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p,hsa-miR-371a-5p, hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975,hsa-miR-6821-5p, hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p,hsa-miR-1228-3p, hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p,hsa-miR-4665-5p, hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p,hsa-miR-3135b, hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476,hsa-miR-4687-3p, hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937,hsa-miR-711, hsa-miR-3141, hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p,hsa-miR-6880-5p, hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p,hsa-miR-4492, hsa-miR-744-5p, hsa-miR-7704, hsa-miR-4749-5p,hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p, hsa-miR-4739,hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p, hsa-miR-373-5p,hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076, hsa-miR-1238-5p,hsa-miR-4463, hsa-miR-4486, hsa-miR-4730, hsa-miR-4286, andhsa-miR-4739.

The kit or the device of the present invention comprises nucleic acidcapable of specifically binding to any of the target nucleic acids asthe early pancreatic cancer or pancreatic cancer precursor lesionmarkers described above, preferably at least one (or one or more)polynucleotide selected from the polynucleotides described in thepreceding Section 2, or a variant thereof.

Specifically, the kit or the device of the present invention cancomprise at least one (or one or more) polynucleotides comprising (orconsisting of) a nucleotide sequence represented by any of SEQ ID NOs: 1to 83, 227 to 229, 246, 248, and 250 or a nucleotide sequence derivedfrom the nucleotide sequence by the replacement of u with t,polynucleotide(s) comprising (or consisting of) a complementary sequencethereof, a polynucleotide(s) hybridizing under stringent conditions toany of these polynucleotides, or a variant(s) or a fragment(s)comprising 15 or more consecutive nucleotides of any of thesepolynucleotide sequences.

The kit or the device of the present invention can further comprise oneor more, two or more, three or more, four or more, or five or morepolynucleotides comprising (or consisting of) a nucleotide sequencerepresented by any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 ora nucleotide sequence derived from the nucleotide sequence by thereplacement of u with t, a polynucleotide(s) comprising (or consistingof) a complementary sequence thereof, a polynucleotide(s) hybridizingunder stringent conditions to any of these polynucleotides, a variant(s)or a fragment(s) comprising 15 or more, 17 or more, or 19 or moreconsecutive nucleotides of any of these polynucleotide sequences.

The fragment or fragments that can be comprised in the kit or the deviceof the present invention is/are, for example, one or more, two or more,three or more, four or more, or five or more polynucleotides selectedfrom the group consisting of the following polynucleotides (1) and (2):

(1) a polynucleotide comprising 15 or more, 17 or more, or 19 or moreconsecutive nucleotides that are from a nucleotide sequence derived froma nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 by the replacement of u with t, or acomplementary sequence thereof; and(2) a polynucleotide comprising 15 or more, 17 or more, or 19 or moreconsecutive nucleotides that are from a nucleotide sequence derived froma nucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230to 245, 247, and 249 by the replacement of u with t, or a complementarysequence thereof.

In a preferred embodiment, the polynucleotide is a polynucleotideconsisting of a nucleotide sequence represented by any of SEQ ID NOs: 1to 83, 227 to 229, 246, 248, and 250 or a nucleotide sequence derivedfrom the nucleotide sequence by the replacement of u with t, apolynucleotide consisting of a complementary sequence thereof, apolynucleotide hybridizing under stringent conditions to any of thesepolynucleotides, or a variant thereof comprising 15 or more, 17 or more,or 19 or more consecutive nucleotides.

In a preferred embodiment, the polynucleotide is a polynucleotideconsisting of a nucleotide sequence represented by any of SEQ ID NOs: 84to 226, 230 to 245, 247, and 249 or a nucleotide sequence derived fromthe nucleotide sequence by the replacement of u with t, a polynucleotideconsisting of a complementary sequence thereof, a polynucleotidehybridizing under stringent conditions to any of these polynucleotides,or a variant thereof comprising 15 or more, 17 or more, or 19 or moreconsecutive nucleotides.

In a preferred embodiment, the fragment can be a polynucleotidecomprising 15 or more, 17 or more, or 19 or more consecutivenucleotides.

In the present invention, the size of the polynucleotide fragment is thenumber of nucleotides in the range from, for example, 15 consecutivenucleotides to less than the total number of nucleotides of thesequence, from 17 consecutive nucleotides to less than the total numberof nucleotides of the sequence, or from 19 consecutive nucleotides toless than the total number of nucleotides of the sequence, in thenucleotide sequence of each polynucleotide.

Specific examples of the aforementioned combination constituting the kitor the device of the present invention can include the above-mentionedpolynucleotides relating to the combinations of SEQ ID NOs shown inTable 1 (i.e., SEQ ID NOs: 1 to 250 corresponding to the miRNA markersin Table 1). However, these are given merely for illustrative purposes,and all of various possible combinations with polynucleotides capable ofspecifically binding to other miRNA markers in Table 1 (corresponding toSEQ ID NOs: 251 to 812) are included in the present invention.

The combination constituting the kit or the device for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject according to the present invention may be, forexample, a combination of two or more, three or more, four or more, orfive or more polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NOs shown in Table 1. Usually, a combination ofeven two of these polynucleotides can produce adequate performance.

The specific combination of two polynucleotides that consist of theabove-mentioned nucleotide sequences or the complementary sequencesthereof for discriminating an early pancreatic cancer or pancreaticcancer precursor lesion patient from a healthy subject is preferably acombination comprising at least one (one or more) polynucleotides of thenewly found polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250, amongthe combinations constituted by two polynucleotides of thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 1 to 250.

The combination of two polynucleotides that consist of theabove-mentioned nucleotide sequences or the complementary sequencesthereof for discriminating an early pancreatic cancer or pancreaticcancer precursor lesion patient from a healthy subject is preferably acombination of a plurality of polynucleotides comprising at least onepolynucleotide selected from the group consisting of polynucleotidesconsisting of the nucleotide sequences represented unlimitedly, forexample, by SEQ ID NOs: 2, 3, 18, 12, 20, 1, 15, 50, 63, 72, 5, 24, 10,52, 9, 11, 19, 39, 61, 7, 17, 22, 26, 74, 21, and 28 or complementarysequences thereof, with any of the polynucleotides of the other SEQ IDNOs.

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 2 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 2 and 18 (markers: hsa-miR-1181 andhsa-miR-6769a-5p);

(2) a combination of SEQ ID NOs: 2 and 53 (markers: hsa-miR-1181 andhsa-miR-3917);

(3) a combination of SEQ ID NOs: 2 and 20 (markers: hsa-miR-1181 andhsa-miR-652-5p);

(4) a combination of SEQ ID NOs: 2 and 3 (markers: hsa-miR-1181 andhsa-miR-671-5p); and

(5) a combination of SEQ ID NOs: 2 and 50 (markers: hsa-miR-1181 andhsa-miR-6746-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 3 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 3 (markers: hsa-miR-6729-5p andhsa-miR-671-5p);

(2) a combination of SEQ ID NOs: 84 and 3 (markers: hsa-miR-1908-5p andhsa-miR-671-5p);

(3) a combination of SEQ ID NOs: 90 and 3 (markers: hsa-miR-3196 andhsa-miR-671-5p);

(4) a combination of SEQ ID NOs: 87 and 3 (markers: hsa-miR-638 andhsa-miR-671-5p); and

(5) a combination of SEQ ID NOs: 3 and 137 (markers: hsa-miR-671-5p andhsa-miR-4673).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 18 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 90 and 18 (markers: hsa-miR-3196 andhsa-miR-6769a-5p);

(2) a combination of SEQ ID NOs: 87 and 18 (markers: hsa-miR-638 andhsa-miR-6769a-5p);

(3) a combination of SEQ ID NOs: 89 and 18 (markers: hsa-miR-3178 andhsa-miR-6769a-5p);

(4) a combination of SEQ ID NOs: 18 and 137 (markers: hsa-miR-6769a-5pand hsa-miR-4673); and

(5) a combination of SEQ ID NOs: 84 and 18 (markers: hsa-miR-1908-5p andhsa-miR-6769a-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 12 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 86 and 12 (markers: hsa-miR-5195-3p andhsa-miR-5090);

(2) a combination of SEQ ID NOs: 109 and 12 (markers: hsa-miR-6769b-5pand hsa-miR-5090);

(3) a combination of SEQ ID NOs: 85 and 12 (markers: hsa-miR-6729-5p andhsa-miR-5090);

(4) a combination of SEQ ID NOs: 88 and 12 (markers: hsa-miR-6125 andhsa-miR-5090); and

(5) a combination of SEQ ID NOs: 105 and 12 (markers: hsa-miR-642a-3pand hsa-miR-5090).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 20 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 20 (markers: hsa-miR-6729-5p andhsa-miR-652-5p);

(2) a combination of SEQ ID NOs: 84 and 20 (markers: hsa-miR-1908-5p andhsa-miR-652-5p);

(3) a combination of SEQ ID NOs: 106 and 20 (markers: hsa-miR-4695-5pand hsa-miR-652-5p);

(4) a combination of SEQ ID NOs: 90 and 20 (markers: hsa-miR-3196 andhsa-miR-652-5p); and

(5) a combination of SEQ ID NOs: 87 and 20 (markers: hsa-miR-638 andhsa-miR-652-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 1 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 1 (markers: hsa-miR-6729-5p andhsa-miR-6784-5p);

(2) a combination of SEQ ID NOs: 87 and 1 (markers: hsa-miR-638 andhsa-miR-6784-5p);

(3) a combination of SEQ ID NOs: 88 and 1 (markers: hsa-miR-6125 andhsa-miR-6784-5p);

(4) a combination of SEQ ID NOs: 86 and 1 (markers: hsa-miR-5195-3p andhsa-miR-6784-5p); and

(5) a combination of SEQ ID NOs: 1 and 3 (markers: hsa-miR-6784-5p andhsa-miR-671-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 15 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 87 and 15 (markers: hsa-miR-638 andhsa-miR-6717-5p);

(2) a combination of SEQ ID NOs: 85 and 15 (markers: hsa-miR-6729-5p andhsa-miR-6717-5p);

(3) a combination of SEQ ID NOs: 2 and 15 (markers: hsa-miR-1181 andhsa-miR-6717-5p);

(4) a combination of SEQ ID NOs: 88 and 15 (markers: hsa-miR-6125 andhsa-miR-6717-5p); and

(5) a combination of SEQ ID NOs: 15 and 137 (markers: hsa-miR-6717-5pand hsa-miR-4673).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 50 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 50 (markers: hsa-miR-6729-5p andhsa-miR-6746-5p);

(2) a combination of SEQ ID NOs: 87 and 50 (markers: hsa-miR-638 andhsa-miR-6746-5p);

(3) a combination of SEQ ID NOs: 84 and 50 (markers: hsa-miR-1908-5p andhsa-miR-6746-5p);

(4) a combination of SEQ ID NOs: 106 and 50 (markers: hsa-miR-4695-5pand hsa-miR-6746-5p); and

(5) a combination of SEQ ID NOs: 90 and 50 (markers: hsa-miR-3196 andhsa-miR-6746-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 63 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 2 and 63 (markers: hsa-miR-1181 andhsa-miR-4419b);

(2) a combination of SEQ ID NOs: 85 and 63 (markers: hsa-miR-6729-5p andhsa-miR-4419b);

(3) a combination of SEQ ID NOs: 90 and 63 (markers: hsa-miR-3196 andhsa-miR-4419b);

(4) a combination of SEQ ID NOs: 84 and 63 (markers: hsa-miR-1908-5p andhsa-miR-4419b); and

(5) a combination of SEQ ID NOs: 87 and 63 (markers: hsa-miR-638 andhsa-miR-4419b).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 72 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 84 and 72 (markers: hsa-miR-1908-5p andhsa-miR-4667-5p);

(2) a combination of SEQ ID NOs: 85 and 72 (markers: hsa-miR-6729-5p andhsa-miR-4667-5p);

(3) a combination of SEQ ID NOs: 88 and 72 (markers: hsa-miR-6125 andhsa-miR-4667-5p);

(4) a combination of SEQ ID NOs: 87 and 72 (markers: hsa-miR-638 andhsa-miR-4667-5p); and

(5) a combination of SEQ ID NOs: 93 and 72 (markers: hsa-miR-4746-3p andhsa-miR-4667-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 5 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 94 and 5 (markers: hsa-miR-4689 andhsa-miR-4276);

(2) a combination of SEQ ID NOs: 85 and 5 (markers: hsa-miR-6729-5p andhsa-miR-4276);

(3) a combination of SEQ ID NOs: 87 and 5 (markers: hsa-miR-638 andhsa-miR-4276);

(4) a combination of SEQ ID NOs: 5 and 107 (markers: hsa-miR-4276 andhsa-miR-7847-3p); and

(5) a combination of SEQ ID NOs: 84 and 5 (markers: hsa-miR-1908-5p andhsa-miR-4276).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 24 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 24 (markers: hsa-miR-6729-5p andhsa-miR-6887-5p);

(2) a combination of SEQ ID NOs: 87 and 24 (markers: hsa-miR-638 andhsa-miR-6887-5p);

(3) a combination of SEQ ID NOs: 89 and 24 (markers: hsa-miR-3178 andhsa-miR-6887-5p);

(4) a combination of SEQ ID NOs: 90 and 24 (markers: hsa-miR-3196 andhsa-miR-6887-5p); and

(5) a combination of SEQ ID NOs: 102 and 24 (markers: hsa-miR-4508 andhsa-miR-6887-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 10 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 10 (markers: hsa-miR-6729-5p andhsa-miR-6795-5p);

(2) a combination of SEQ ID NOs: 87 and 10 (markers: hsa-miR-638 andhsa-miR-6795-5p);

(3) a combination of SEQ ID NOs: 90 and 10 (markers: hsa-miR-3196 andhsa-miR-6795-5p);

(4) a combination of SEQ ID NOs: 88 and 10 (markers: hsa-miR-6125 andhsa-miR-6795-5p); and

(5) a combination of SEQ ID NOs: 2 and 10 (markers: hsa-miR-1181 andhsa-miR-6795-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 52 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 52 (markers: hsa-miR-6729-5p andhsa-miR-4688);

(2) a combination of SEQ ID NOs: 88 and 52 (markers: hsa-miR-6125 andhsa-miR-4688);

(3) a combination of SEQ ID NOs: 87 and 52 (markers: hsa-miR-638 andhsa-miR-4688);

(4) a combination of SEQ ID NOs: 98 and 52 (markers: hsa-miR-6724-5p andhsa-miR-4688); and

(5) a combination of SEQ ID NOs: 84 and 52 (markers: hsa-miR-1908-5p andhsa-miR-4688).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 9 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 87 and 9 (markers: hsa-miR-638 andhsa-miR-4675);

(2) a combination of SEQ ID NOs: 89 and 9 (markers: hsa-miR-3178 andhsa-miR-4675);

(3) a combination of SEQ ID NOs: 85 and 9 (markers: hsa-miR-6729-5p andhsa-miR-4675);

(4) a combination of SEQ ID NOs: 117 and 9 (markers: hsa-miR-4787-5p andhsa-miR-4675); and

(5) a combination of SEQ ID NOs: 88 and 9 (markers: hsa-miR-6125 andhsa-miR-4675).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 11 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 87 and 11 (markers: hsa-miR-638 andhsa-miR-4731-5p);

(2) a combination of SEQ ID NOs: 85 and 11 (markers: hsa-miR-6729-5p andhsa-miR-4731-5p);

(3) a combination of SEQ ID NOs: 89 and 11 (markers: hsa-miR-3178 andhsa-miR-4731-5p);

(4) a combination of SEQ ID NOs: 102 and 11 (markers: hsa-miR-4508 andhsa-miR-4731-5p); and

(5) a combination of SEQ ID NOs: 84 and 11 (markers: hsa-miR-1908-5p andhsa-miR-4731-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 19 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 19 (markers: hsa-miR-6729-5p andhsa-miR-4728-5p);

(2) a combination of SEQ ID NOs: 87 and 19 (markers: hsa-miR-638 andhsa-miR-4728-5p);

(3) a combination of SEQ ID NOs: 88 and 19 (markers: hsa-miR-6125 andhsa-miR-4728-5p);

(4) a combination of SEQ ID NOs: 89 and 19 (markers: hsa-miR-3178 andhsa-miR-4728-5p); and

(5) a combination of SEQ ID NOs: 106 and 19 (markers: hsa-miR-4695-5pand hsa-miR-4728-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 39 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 87 and 39 (markers: hsa-miR-638 andhsa-miR-6861-5p);

(2) a combination of SEQ ID NOs: 85 and 39 (markers: hsa-miR-6729-5p andhsa-miR-6861-5p);

(3) a combination of SEQ ID NOs: 88 and 39 (markers: hsa-miR-6125 andhsa-miR-6861-5p);

(4) a combination of SEQ ID NOs: 84 and 39 (markers: hsa-miR-1908-5p andhsa-miR-6861-5p); and

(5) a combination of SEQ ID NOs: 2 and 39 (markers: hsa-miR-1181 andhsa-miR-6861-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 61 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 87 and 61 (markers: hsa-miR-638 andhsa-miR-498);

(2) a combination of SEQ ID NOs: 85 and 61 (markers: hsa-miR-6729-5p andhsa-miR-498);

(3) a combination of SEQ ID NOs: 88 and 61 (markers: hsa-miR-6125 andhsa-miR-498);

(4) a combination of SEQ ID NOs: 108 and 61 (markers: hsa-miR-3197 andhsa-miR-498); and

(5) a combination of SEQ ID NOs: 93 and 61 (markers: hsa-miR-4746-3p andhsa-miR-498).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 7 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 88 and 7 (markers: hsa-miR-6125 andhsa-miR-149-3p);

(2) a combination of SEQ ID NOs: 85 and 7 (markers: hsa-miR-6729-5p andhsa-miR-149-3p);

(3) a combination of SEQ ID NOs: 87 and 7 (markers: hsa-miR-638 andhsa-miR-149-3p);

(4) a combination of SEQ ID NOs: 86 and 7 (markers: hsa-miR-5195-3p andhsa-miR-149-3p); and

(5) a combination of SEQ ID NOs: 91 and 7 (markers: hsa-miR-8069 andhsa-miR-149-3p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 17 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 17 (markers: hsa-miR-6729-5p andhsa-miR-6738-5p);

(2) a combination of SEQ ID NOs: 87 and 17 (markers: hsa-miR-638 andhsa-miR-6738-5p);

(3) a combination of SEQ ID NOs: 89 and 17 (markers: hsa-miR-3178 andhsa-miR-6738-5p);

(4) a combination of SEQ ID NOs: 102 and 17 (markers: hsa-miR-4508 andhsa-miR-6738-5p); and

(5) a combination of SEQ ID NOs: 84 and 17 (markers: hsa-miR-1908-5p andhsa-miR-6738-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 22 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 22 (markers: hsa-miR-6729-5p andhsa-miR-6785-5p);

(2) a combination of SEQ ID NOs: 87 and 22 (markers: hsa-miR-638 andhsa-miR-6785-5p);

(3) a combination of SEQ ID NOs: 102 and 22 (markers: hsa-miR-4508 andhsa-miR-6785-5p);

(4) a combination of SEQ ID NOs: 89 and 22 (markers: hsa-miR-3178 andhsa-miR-6785-5p); and

(5) a combination of SEQ ID NOs: 117 and 22 (markers: hsa-miR-4787-5pand hsa-miR-6785-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 26 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 26 (markers: hsa-miR-6729-5p andhsa-miR-1228-5p);

(2) a combination of SEQ ID NOs: 87 and 26 (markers: hsa-miR-638 andhsa-miR-1228-5p);

(3) a combination of SEQ ID NOs: 88 and 26 (markers: hsa-miR-6125 andhsa-miR-1228-5p);

(4) a combination of SEQ ID NOs: 84 and 26 (markers: hsa-miR-1908-5p andhsa-miR-1228-5p); and

(5) a combination of SEQ ID NOs: 94 and 26 (markers: hsa-miR-4689 andhsa-miR-1228-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 74 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 74 (markers: hsa-miR-6729-5p andhsa-miR-4690-5p);

(2) a combination of SEQ ID NOs: 2 and 74 (markers: hsa-miR-1181 andhsa-miR-4690-5p);

(3) a combination of SEQ ID NOs: 87 and 74 (markers: hsa-miR-638 andhsa-miR-4690-5p);

(4) a combination of SEQ ID NOs: 84 and 74 (markers: hsa-miR-1908-5p andhsa-miR-4690-5p); and

(5) a combination of SEQ ID NOs: 88 and 74 (markers: hsa-miR-6125 andhsa-miR-4690-5p).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 21 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 90 and 21 (markers: hsa-miR-3196 andhsa-miR-4257);

(2) a combination of SEQ ID NOs: 2 and 21 (markers: hsa-miR-1181 andhsa-miR-4257);

(3) a combination of SEQ ID NOs: 106 and 21 (markers: hsa-miR-4695-5pand hsa-miR-4257);

(4) a combination of SEQ ID NOs: 84 and 21 (markers: hsa-miR-1908-5p andhsa-miR-4257); and

(5) a combination of SEQ ID NOs: 85 and 21 (markers: hsa-miR-6729-5p andhsa-miR-4257).

Non-limiting examples of the combination comprising a polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 28 or acomplementary sequence thereof among the combinations constituted by twopolynucleotides of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 250 for discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject are listed below:

(1) a combination of SEQ ID NOs: 85 and 28 (markers: hsa-miR-6729-5p andhsa-miR-6782-5p);

(2) a combination of SEQ ID NOs: 84 and 28 (markers: hsa-miR-1908-5p andhsa-miR-6782-5p);

(3) a combination of SEQ ID NOs: 86 and 28 (markers: hsa-miR-5195-3p andhsa-miR-6782-5p);

(4) a combination of SEQ ID NOs: 87 and 28 (markers: hsa-miR-638 andhsa-miR-6782-5p); and

(5) a combination of SEQ ID NOs: 93 and 28 (markers: hsa-miR-4746-3p andhsa-miR-6782-5p).

The combination of polynucleotides with cancer type specificity capableof discriminating an early pancreatic cancer or pancreatic cancerprecursor lesion patient not only from a healthy subject but also frompatients with other cancers is preferably unlimitedly, for example, acombination of multiple polynucleotides comprising: at least onepolynucleotide selected from the group consisting of polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 119,12, 28, 105, 137, 121, 109, 87, 5, 140, 106, 2, 175, 90, 237, 247, 103,97, 124, 92, 100, 32, 1, 246, 84, 13, 85, 153, 111, 86, 141, 54, and 24or complementary sequences thereof (hereinafter, this group is referredto as “cancer type-specific polynucleotide group 1”); and any of thepolynucleotides of the other SEQ ID NOs.

The combination of polynucleotides with cancer type specificity capableof discriminating an early pancreatic cancer or pancreatic cancerprecursor lesion patient not only from a healthy subject but also frompatients with other cancers is more preferably a combination of multiplepolynucleotides selected from the cancer type-specific polynucleotidegroup 1.

The combination of polynucleotides with cancer type specificity capableof discriminating an early pancreatic cancer or pancreatic cancerprecursor lesion patient not only from a healthy subject but also frompatients with other cancers is more preferably, for example, acombination of polynucleotides comprising at least one polynucleotidesselected from the group consisting of polynucleotides consisting of thenucleotide sequences represented by, for example, SEQ ID NOs: 119, 12,28, 105, 137, 121, 109, 87, 5, 140, 106, 2, 175, 90, 237, and 247 orcomplementary sequences thereof (hereinafter, this group is referred toas “cancer type-specific polynucleotide group 2”) included in the cancertype-specific polynucleotide group 1, among the combinations of multiplepolynucleotides selected from the cancer type-specific polynucleotidegroup 1. The number of the polynucleotides with cancer type specificitymay be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more in the combination and ismore preferably 5 or more in the combination. Usually, the combinationof 5 polynucleotides of these polynucleotides can produce sufficientperformance (such as accuracy, sensitivity, or specificity).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NO: 12 orcomplementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 12, 137, 119, 105, and 237 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-373-5p);

(2) a combination of SEQ ID NOs: 87, 12, 137, 119, and 105 (markers:hsa-miR-638, hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(3) a combination of SEQ ID NOs: 12, 103, 137, 105, and 247 (markers:hsa-miR-5090, hsa-miR-6085, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-4286);

(4) a combination of SEQ ID NOs: 12, 137, 119, 92, and 105 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-4723-5p, andhsa-miR-642a-3p);

(5) a combination of SEQ ID NOs: 12, 137, 119, 105, and 121 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-602);

(6) a combination of SEQ ID NOs: 12, 137, 1, 119, and 105 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6784-5p, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(7) a combination of SEQ ID NOs: 12, 137, 119, 124, and 105 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-5100, andhsa-miR-642a-3p);

(8) a combination of SEQ ID NOs: 12, 137, 119, 105, and 32 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6087);

(9) a combination of SEQ ID NOs: 12, 137, 119, 105, and 100 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6875-5p);

(10) a combination of SEQ ID NOs: 12, 137, 119, 105, and 86 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-5195-3p);

(11) a combination of SEQ ID NOs: 12, 137, 119, 105, and 153 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-296-5p);

(12) a combination of SEQ ID NOs: 12, 137, 119, 105, and 141 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-663a);

(13) a combination of SEQ ID NOs: 12, 137, 105, 246, and 153 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6766-3p, andhsa-miR-296-5p);

(14) a combination of SEQ ID NOs: 12, 97, 137, 105, and 153 (markers:hsa-miR-5090, hsa-miR-7109-5p, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-296-5p);

(15) a combination of SEQ ID NOs: 12, 103, 137, 119, and 105 (markers:hsa-miR-5090, hsa-miR-6085, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(16) a combination of SEQ ID NOs: 12, 137, 119, 105, and 246 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6766-3p);

(17) a combination of SEQ ID NOs: 12, 137, 92, 105, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-4723-5p, hsa-miR-642a-3p, andhsa-miR-4286);

(18) a combination of SEQ ID NOs: 12, 137, 124, 105, and 153 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-5100, hsa-miR-642a-3p, andhsa-miR-296-5p);

(19) a combination of SEQ ID NOs: 12, 137, 105, 32, and 153 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6087, andhsa-miR-296-5p);

(20) a combination of SEQ ID NOs: 12, 137, 105, 13, and 121 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-3620-5p, andhsa-miR-602);

(21) a combination of SEQ ID NOs: 106, 12, 137, 119, and 105 (markers:hsa-miR-4695-5p, hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(22) a combination of SEQ ID NOs: 12, 137, 119, 105, and 13 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-3620-5p);

(23) a combination of SEQ ID NOs: 12, 137, 119, 105, and 140 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-4640-5p);

(24) a combination of SEQ ID NOs: 12, 137, 119, 105, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-4286);

(25) a combination of SEQ ID NOs: 12, 137, 119, 105, and 109 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6769b-5p);

(26) a combination of SEQ ID NOs: 12, 137, 105, 109, and 121 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6769b-5p, andhsa-miR-602);

(27) a combination of SEQ ID NOs: 12, 103, 137, 105, and 121 (markers:hsa-miR-5090, hsa-miR-6085, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-602);

(28) a combination of SEQ ID NOs: 12, 137, 105, 32, and 121 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6087, andhsa-miR-602);

(29) a combination of SEQ ID NOs: 12, 137, 124, 105, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-5100, hsa-miR-642a-3p, andhsa-miR-4286);

(30) a combination of SEQ ID NOs: 12, 137, 105, 246, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6766-3p, andhsa-miR-4286);

(31) a combination of SEQ ID NOs: 12, 137, 105, 153, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-296-5p, andhsa-miR-4286);

(32) a combination of SEQ ID NOs: 12, 137, 105, 247, and 141 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-4286, andhsa-miR-663a);

(33) a combination of SEQ ID NOs: 12, 137, 105, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, and hsa-miR-4286);

(34) a combination of SEQ ID NOs: 12, 137, 105, 140, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-4640-5p, andhsa-miR-4286);

(35) a combination of SEQ ID NOs: 12, 119, 124, 105, and 140 (markers:hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-5100, hsa-miR-642a-3p, andhsa-miR-4640-5p);

(36) a combination of SEQ ID NOs: 12, 119, 105, 100, and 140 (markers:hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-642a-3p, hsa-miR-6875-5p, andhsa-miR-4640-5p);

(37) a combination of SEQ ID NOs: 90, 12, 119, 105, and 140 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-4640-5p);

(38) a combination of SEQ ID NOs: 90, 12, 137, 119, and 105 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(39) a combination of SEQ ID NOs: 90, 12, 137, 105, and 32 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-6087);

(40) a combination of SEQ ID NOs: 90, 12, 137, 105, and 153 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-296-5p);

(41) a combination of SEQ ID NOs: 90, 12, 119, 105, and 100 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6875-5p);

(42) a combination of SEQ ID NOs: 90, 12, 119, 109, and 140 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-6769b-5p, andhsa-miR-4640-5p);

(43) a combination of SEQ ID NOs: 87, 12, 137, 105, and 247 (markers:hsa-miR-638, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-4286);

(44) a combination of SEQ ID NOs: 90, 12, 109, 140, and 237 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-6769b-5p, hsa-miR-4640-5p, andhsa-miR-373-5p);

(45) a combination of SEQ ID NOs: 12, 137, 105, 109, and 153 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6769b-5p, andhsa-miR-296-5p);

(46) a combination of SEQ ID NOs: 12, 137, 105, 109, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6769b-5p, andhsa-miR-4286);

(47) a combination of SEQ ID NOs: 12, 137, 109, 140, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6769b-5p, hsa-miR-4640-5p, andhsa-miR-4286);

(48) a combination of SEQ ID NOs: 12, 137, 109, 121, and 237 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6769b-5p, hsa-miR-602, andhsa-miR-373-5p);

(49) a combination of SEQ ID NOs: 12, 137, 119, 105, and 175 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6768-5p);

(50) a combination of SEQ ID NOs: 12, 137, 109, 175, and 121 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6769b-5p, hsa-miR-6768-5p, andhsa-miR-602);

(51) a combination of SEQ ID NOs: 87, 12, 119, 105, and 175 (markers:hsa-miR-638, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6768-5p);

(52) a combination of SEQ ID NOs: 12, 137, 119, 105, and 111 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-187-5p);

(53) a combination of SEQ ID NOs: 12, 137, 119, 105, and 24 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6887-5p);

(54) a combination of SEQ ID NOs: 12, 137, 105, 32, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6087, andhsa-miR-4286);

(55) a combination of SEQ ID NOs: 90, 12, 137, 105, and 237 (markers:hsa-miR-3196, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-373-5p);

(56) a combination of SEQ ID NOs: 12, 84, 137, 119, and 105 (markers:hsa-miR-5090, hsa-miR-1908-5p, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(57) a combination of SEQ ID NOs: 12, 97, 137, 105, and 247 (markers:hsa-miR-5090, hsa-miR-7109-5p, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-4286);

(58) a combination of SEQ ID NOs: 87, 12, 137, 105, and 237 (markers:hsa-miR-638, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-373-5p);

(59) a combination of SEQ ID NOs: 87, 12, 100, 109, and 237 (markers:hsa-miR-638, hsa-miR-5090, hsa-miR-6875-5p, hsa-miR-6769b-5p, andhsa-miR-373-5p);

(60) a combination of SEQ ID NOs: 87, 12, 100, 109, and 237 (markers:hsa-miR-638, hsa-miR-5090, hsa-miR-6875-5p, hsa-miR-6769b-5p, andhsa-miR-373-5p);

(61) a combination of SEQ ID NOs: 106, 12, 137, 105, and 86 (markers:hsa-miR-4695-5p, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-5195-3p);

(62) a combination of SEQ ID NOs: 106, 12, 137, 105, and 247 (markers:hsa-miR-4695-5p, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-4286);

(63) a combination of SEQ ID NOs: 106, 12, 119, 105, and 100 (markers:hsa-miR-4695-5p, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6875-5p); and

(64) a combination of SEQ ID NOs: 106, 12, 137, 105, and 121 (markers:hsa-miR-4695-5p, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-602).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NO: 28 orcomplementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 137, 119, 105, 28, and 237 (markers:hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, hsa-miR-6782-5p, andhsa-miR-373-5p);

(2) a combination of SEQ ID NOs: 87, 106, 119, 28, and 121 (markers:hsa-miR-638, hsa-miR-4695-5p, hsa-miR-6813-5p, hsa-miR-6782-5p, andhsa-miR-602);

(3) a combination of SEQ ID NOs: 106, 137, 119, 28, and 121 (markers:hsa-miR-4695-5p, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-6782-5p, andhsa-miR-602); and

(4) a combination of SEQ ID NOs: 90, 119, 105, 28, and 237 (markers:hsa-miR-3196, hsa-miR-6813-5p, hsa-miR-642a-3p, hsa-miR-6782-5p, andhsa-miR-373-5p).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NO: 5 orcomplementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 90, 5, 137, 119, and 105 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(2) a combination of SEQ ID NOs: 5, 137, 119, 105, and 237 (markers:hsa-miR-4276, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-373-5p); and

(3) a combination of SEQ ID NOs: 5, 137, 119, 105, and 32 (markers:hsa-miR-4276, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6087).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NO: 2 orcomplementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 2, 137, 119, 105, and 237 (markers:hsa-miR-1181, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-373-5p);

(2) a combination of SEQ ID NOs: 2, 87, 137, 119, and 105 (markers:hsa-miR-1181, hsa-miR-638, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(3) a combination of SEQ ID NOs: 2, 137, 119, 105, and 13 (markers:hsa-miR-1181, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-3620-5p);

(4) a combination of SEQ ID NOs: 2, 137, 119, 105, and 121 (markers:hsa-miR-1181, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-602);

(5) a combination of SEQ ID NOs: 2, 137, 119, 105, and 247 (markers:hsa-miR-1181, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-4286);

(6) a combination of SEQ ID NOs: 2, 87, 119, 109, and 247 (markers:hsa-miR-1181, hsa-miR-638, hsa-miR-6813-5p, hsa-miR-6769b-5p, andhsa-miR-4286);

(7) a combination of SEQ ID NOs: 2, 90, 137, 119, and 105 (markers:hsa-miR-1181, hsa-miR-3196, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(8) a combination of SEQ ID NOs: 2, 137, 119, 105, and 140 (markers:hsa-miR-1181, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-4640-5p); and

(9) a combination of SEQ ID NOs: 2, 87, 119, 105, and 237 (markers:hsa-miR-1181, hsa-miR-638, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-373-5p).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 12 and28 or complementary sequences thereof, with polynucleotides consistingof nucleotide sequences represented by SEQ ID NOs of fivepolynucleotides selected from the cancer type-specific polynucleotidegroup 1 or complementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 12, 137, 105, 28, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, hsa-miR-6782-5p, andhsa-miR-4286);

(2) a combination of SEQ ID NOs: 12, 137, 119, 105, and 28 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-6782-5p);

(3) a combination of SEQ ID NOs: 12, 103, 137, 105, and 28 (markers:hsa-miR-5090, hsa-miR-6085, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-6782-5p);

(4) a combination of SEQ ID NOs: 12, 84, 28, 140, and 121 (markers:hsa-miR-5090, hsa-miR-1908-5p, hsa-miR-6782-5p, hsa-miR-4640-5p, andhsa-miR-602);

(5) a combination of SEQ ID NOs: 12, 137, 28, 109, and 121 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6782-5p, hsa-miR-6769b-5p, andhsa-miR-602);

(6) a combination of SEQ ID NOs: 12, 1, 28, 121, and 247 (markers:hsa-miR-5090, hsa-miR-6784-5p, hsa-miR-6782-5p, hsa-miR-602, andhsa-miR-4286);

(7) a combination of SEQ ID NOs: 12, 119, 28, 100, and 121 (markers:hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-6782-5p, hsa-miR-6875-5p, andhsa-miR-602);

(8) a combination of SEQ ID NOs: 12, 92, 28, 100, and 247 (markers:hsa-miR-5090, hsa-miR-4723-5p, hsa-miR-6782-5p, hsa-miR-6875-5p, andhsa-miR-4286);

(9) a combination of SEQ ID NOs: 12, 28, 100, 140, and 247 (markers:hsa-miR-5090, hsa-miR-6782-5p, hsa-miR-6875-5p, hsa-miR-4640-5p, andhsa-miR-4286);

(10) a combination of SEQ ID NOs: 12, 137, 28, 109, and 247 (markers:hsa-miR-5090, hsa-miR-4673, hsa-miR-6782-5p, hsa-miR-6769b-5p, andhsa-miR-4286);

(11) a combination of SEQ ID NOs: 12, 84, 28, 109, and 121 (markers:hsa-miR-5090, hsa-miR-1908-5p, hsa-miR-6782-5p, hsa-miR-6769b-5p, andhsa-miR-602);

(12) a combination of SEQ ID NOs: 12, 103, 1, 28, and 121 (markers:hsa-miR-5090, hsa-miR-6085, hsa-miR-6784-5p, hsa-miR-6782-5p, andhsa-miR-602);

(13) a combination of SEQ ID NOs: 12, 1, 28, 32, and 121 (markers:hsa-miR-5090, hsa-miR-6784-5p, hsa-miR-6782-5p, hsa-miR-6087, andhsa-miR-602);

(14) a combination of SEQ ID NOs: 12, 1, 28, 100, and 121 (markers:hsa-miR-5090, hsa-miR-6784-5p, hsa-miR-6782-5p, hsa-miR-6875-5p, andhsa-miR-602); and

(15) a combination of SEQ ID NOs: 12, 1, 28, 175, and 121 (markers:hsa-miR-5090, hsa-miR-6784-5p, hsa-miR-6782-5p, hsa-miR-6768-5p, andhsa-miR-602).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 12 and5 or complementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 5, 12, 137, 119, and 105 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(2) a combination of SEQ ID NOs: 90, 5, 12, 119, and 105 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(3) a combination of SEQ ID NOs: 5, 12, 137, 105, and 121 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-602);

(4) a combination of SEQ ID NOs: 5, 12, 119, 92, and 121 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-4723-5p, andhsa-miR-602);

(5) a combination of SEQ ID NOs: 90, 5, 12, 109, and 247 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-6769b-5p, andhsa-miR-4286);

(6) a combination of SEQ ID NOs: 5, 12, 137, 109, and 121 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, hsa-miR-6769b-5p, andhsa-miR-602);

(7) a combination of SEQ ID NOs: 5, 12, 137, 109, and 247 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, hsa-miR-6769b-5p, andhsa-miR-4286);

(8) a combination of SEQ ID NOs: 90, 5, 106, 12, and 109 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-4695-5p, hsa-miR-5090, andhsa-miR-6769b-5p);

(9) a combination of SEQ ID NOs: 90, 5, 12, 137, and 105 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, andhsa-miR-642a-3p);

(10) a combination of SEQ ID NOs: 90, 5, 12, 119, and 109 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-6813-5p, andhsa-miR-6769b-5p);

(11) a combination of SEQ ID NOs: 90, 5, 12, 105, and 109 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-642a-3p, andhsa-miR-6769b-5p);

(12) a combination of SEQ ID NOs: 5, 12, 137, 105, and 153 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-296-5p);

(13) a combination of SEQ ID NOs: 5, 12, 119, 105, and 54 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-6813-5p, hsa-miR-642a-3p, andhsa-miR-5787);

(14) a combination of SEQ ID NOs: 87, 5, 106, 12, and 109 (markers:hsa-miR-638, hsa-miR-4276, hsa-miR-4695-5p, hsa-miR-5090, andhsa-miR-6769b-5p);

(15) a combination of SEQ ID NOs: 87, 5, 12, 137, and 105 (markers:hsa-miR-638, hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, andhsa-miR-642a-3p);

(16) a combination of SEQ ID NOs: 90, 5, 12, 1, and 105 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-6784-5p, andhsa-miR-642a-3p);

(17) a combination of SEQ ID NOs: 90, 5, 12, 109, and 86 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-6769b-5p, andhsa-miR-5195-3p);

(18) a combination of SEQ ID NOs: 5, 12, 137, 105, and 247 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-4286);

(19) a combination of SEQ ID NOs: 90, 5, 12, 109, and 175 (markers:hsa-miR-3196, hsa-miR-4276, hsa-miR-5090, hsa-miR-6769b-5p, andhsa-miR-6768-5p); and

(20) a combination of SEQ ID NOs: 5, 12, 100, 109, and 121 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-6875-5p, hsa-miR-6769b-5p, andhsa-miR-602).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 12 and2 or complementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 2, 12, 137, 119, and 105 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-4673, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(2) a combination of SEQ ID NOs: 2, 12, 137, 105, and 153 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-296-5p);

(3) a combination of SEQ ID NOs: 2, 12, 137, 105, and 121 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-602);

(4) a combination of SEQ ID NOs: 2, 12, 109, 121, and 247 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-6769b-5p, hsa-miR-602, andhsa-miR-4286);

(5) a combination of SEQ ID NOs: 2, 90, 12, 119, and 105 (markers:hsa-miR-1181, hsa-miR-3196, hsa-miR-5090, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(6) a combination of SEQ ID NOs: 2, 90, 12, 109, and 140 (markers:hsa-miR-1181, hsa-miR-3196, hsa-miR-5090, hsa-miR-6769b-5p, andhsa-miR-4640-5p);

(7) a combination of SEQ ID NOs: 2, 12, 100, 109, and 121 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-6875-5p, hsa-miR-6769b-5p, andhsa-miR-602);

(8) a combination of SEQ ID NOs: 2, 12, 109, 175, and 121 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-6769b-5p, hsa-miR-6768-5p, andhsa-miR-602);

(9) a combination of SEQ ID NOs: 2, 12, 97, 105, and 247 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-7109-5p, hsa-miR-642a-3p, andhsa-miR-4286);

(10) a combination of SEQ ID NOs: 2, 12, 137, 105, and 247 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-4673, hsa-miR-642a-3p, andhsa-miR-4286); and

(11) a combination of SEQ ID NOs: 2, 12, 137, 109, and 121 (markers:hsa-miR-1181, hsa-miR-5090, hsa-miR-4673, hsa-miR-6769b-5p, andhsa-miR-602).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 5 and2 or complementary sequences thereof, with polynucleotides consisting ofnucleotide sequences represented by SEQ ID NOs of five polynucleotidesselected from the cancer type-specific polynucleotide group 1 orcomplementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 2, 90, 5, 119, and 105 (markers:hsa-miR-1181, hsa-miR-3196, hsa-miR-4276, hsa-miR-6813-5p, andhsa-miR-642a-3p);

(2) a combination of SEQ ID NOs: 2, 5, 119, 109, and 121 (markers:hsa-miR-1181, hsa-miR-4276, hsa-miR-6813-5p, hsa-miR-6769b-5p, andhsa-miR-602); and

(3) a combination of SEQ ID NOs: 2, 5, 119, 86, and 121 (markers:hsa-miR-1181, hsa-miR-4276, hsa-miR-6813-5p, hsa-miR-5195-3p, andhsa-miR-602).

Non-limiting examples of the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 12,28, and 5 or complementary sequences thereof, with polynucleotidesconsisting of nucleotide sequences represented by SEQ ID NOs of fivepolynucleotides selected from the cancer type-specific polynucleotidegroup 1 or complementary sequences thereof are further listed below:

(1) a combination of SEQ ID NOs: 5, 12, 1, 28, and 121 (markers:hsa-miR-4276, hsa-miR-5090, hsa-miR-6784-5p, hsa-miR-6782-5p, andhsa-miR-602).

The kit or the device of the present invention can also comprise a knownpolynucleotide(s) that enables detection of early pancreatic cancer or apancreatic cancer precursor lesion, or a polynucleotide(s) that will befound in the future, in addition to the polynucleotide(s) (which mayinclude a variant(s), a fragment(s), or a derivative(s)) as describedabove according to the present invention.

The kit of the present invention can also comprise an antibody formeasuring a marker or markers for examination of early pancreatic canceror pancreatic cancer precursor lesion known in the art, such as CEA,CA19-9, SPan-1, DUPAN-2, CA50, CA242, TAG-72, urinary fucose, POA, andTPS, in addition to the polynucleotide(s) according to the presentinvention as described above, and a variant or variants thereof or afragment or fragments thereof.

These polynucleotides and variants thereof or fragments thereofcontained in the kit of the present invention may be packaged indifferent containers either individually or in any combination.

The kit of the present invention may comprise a kit for extractingnucleic acids (e.g., total RNA) from body fluids, cells, or tissues, afluorescent material for labeling, an enzyme and a medium for nucleicacid amplification, an instruction manual, etc.

The device of the present invention is a device for cancer markermeasurement in which nucleic acids such as the polynucleotides accordingto the present invention described above, variants thereof, derivativesthereof, or fragments thereof are linked or attached to, for example, asolid phase. Examples of the material for the solid phase includeplastics, paper, glass, and silicon. The material for the solid phase ispreferably a plastic from the viewpoint of easy processability. Thesolid phase has any shape and is, for example, square, round,reed-shaped, or film-shaped. The device of the present inventionincludes, for example, a device for measurement by a hybridizationtechnique. Specific examples thereof include blotting devices andnucleic acid arrays (e.g., microarrays, DNA chips, and RNA chips).

The nucleic acid array technique is a technique which involves linkingor attaching the nucleic acids one by one by use of a method [e.g., amethod of spotting the nucleic acids using a high-density dispensercalled spotter or arrayer onto the surface of the solid phasesurface-treated, if necessary, by L-lysine coating or the introductionof a functional group such as an amino group or a carboxyl group, amethod of spraying the nucleic acids onto the solid phase using aninkjet which injects very small liquid droplets by a piezoelectricelement or the like from a nozzle, or a method of sequentiallysynthesizing nucleotides on the solid phase] to prepare an array such asa chip and measuring target nucleic acids through the use ofhybridization using this array.

The kit or the device of the present invention comprises nucleic acidscapable of specifically binding to the polynucleotides of at least one,preferably at least two, more preferably at least three, most preferablyat least five to all of the early pancreatic cancer or pancreatic cancerprecursor lesion marker miRNAs, respectively, of the group 1 describedabove. The kit or the device of the present invention can optionallyfurther comprise nucleic acids capable of specifically binding to thepolynucleotides of at least one, preferably at least two, morepreferably at least three, most preferably at least five to all of theearly pancreatic cancer or pancreatic cancer precursor lesion markermiRNAs, respectively, of the group 2 described above.

The kit or the device of the present invention can be used for detectingearly pancreatic cancer or a pancreatic cancer precursor lesion asdescribed in Section 4 below.

4. Method for Detecting Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion

The present invention further provides a method for detecting earlypancreatic cancer or a pancreatic cancer precursor lesion in a subject,comprising using the kit or the device of the present invention(comprising the above-mentioned nucleic acid(s) that can be used in thepresent invention) as described in Section 3 above to measure anexpression level of at least one early pancreatic cancer or pancreaticcancer precursor lesion-derived gene selected from the following groupof miRNAs, i.e., miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p,miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p,miR-4731-5p, miR-5090, miR-3620-5p, miR-1343-5p, miR-6717-5p,miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p,miR-4257, miR-6785-5p, miR-7110-5p, miR-6887-5p, miR-887-3p,miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p,miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p,miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p,miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p,miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688,miR-3917, miR-5787, miR-4632-5p, miR-6126, miR-135a-3p, miR-8063,miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p,miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p,miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920,miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p,miR-4447, miR-6869-5p, miR-6794-5p, miR-6511a-5p, miR-6824-5p,miR-6766-3p, miR-6511a-5p, and miR-6749-5p, and optionally an expressionlevel of at least one early pancreatic cancer or pancreatic cancerprecursor lesion-derived gene selected from the following group ofmiRNAs, i.e., miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125,miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689,miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p,miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p,miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p,miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p,miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p,miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718,miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p,miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a,miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449,miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p,miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p,miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p,miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p,miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p,miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513,miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p,miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975,miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p,miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505,miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476,miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141,miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648,miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-762,miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p,miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p,miR-4463, miR-4486, miR-4730, miR-4286, and miR-4739 in a sample such asblood, serum, or plasma in vitro; and comparing, for example, theexpression levels having statistically significant difference using theexpression level(s) thus measured and a control expression level(s) in ahealthy subject(s) (including a non-pancreatic cancer patient(s) and anon-pancreatic cancer precursor lesion patient(s)) measured in the sameway, or evaluating in vitro whether the subject has early pancreaticcancer or a pancreatic cancer precursor lesion on the basis of adiscriminant score determined from the expression level(s) of thegene(s) in the sample and a discriminant (see below), to detect thepresence or absence of early pancreatic cancer or a pancreatic cancerprecursor lesion in the subject.

This method of the present invention enables a minimally invasive, earlydiagnosis of the cancer with high sensitivity and high specificity andthereby brings about early treatment and improved prognosis. Inaddition, exacerbation of the disease or the effectiveness of surgical,radiotherapeutic, and chemotherapeutic treatments can be monitored.

The method for extracting the early pancreatic cancer or pancreaticcancer precursor lesion-derived gene(s) from the sample such as blood,serum, or plasma according to the present invention is particularlypreferably prepared by the addition of a reagent for RNA extraction in3D-Gene® RNA extraction reagent from liquid sample kit (TorayIndustries, Inc.). A general acidic phenol method (acidguanidinium-phenol-chloroform (AGPC) method) may be used, or Trizol®(Life Technologies Corp.) may be used. The pancreatic cancer orpancreatic cancer precursor lesion-derived gene(s) may be prepared bythe addition of a reagent for RNA extraction containing acidic phenol,such as Trizol (Life Technologies Corp.) or Isogen (Nippon Gene Co.,Ltd., Japan). Alternatively, a kit such as miRNeasy® Mini Kit (QiagenN.V.) may be used, though the method is not limited thereto.

The present invention also provides use of the kit or the device of thepresent invention for detecting in vitro an expression product(s) of anearly pancreatic cancer or pancreatic cancer precursor lesion-derivedmiRNA gene(s) in a sample derived from a subject.

In the method of the present invention, the kit or the device describedabove comprises a single polynucleotide or any possible combination ofpolynucleotides that can be used in the present invention as describedabove.

In the detection or (genetic) diagnosis of early pancreatic cancer or apancreatic cancer precursor lesion according to the present invention,each polynucleotide contained in the kit or the device of the presentinvention can be used as a probe or a primer. In the case of using thepolynucleotide as a primer, TaqMan® MicroRNA Assays from LifeTechnologies Corp., miScript PCR System from Qiagen N.V., or the likecan be used, though the method is not limited thereto.

The polynucleotide contained in the kit or the device of the presentinvention can be used as a primer or a probe according to a routinemethod in a method known in the art for specifically detecting aparticular gene, for example, a hybridization technique such as Northernblot, Southern blot, in situ hybridization, Northern hybridization, orSouthern hybridization, a polynucleotide sequencing technique using asequencer or the like, or a quantitative amplification technique such asquantitative RT-PCR. A body fluid such as blood, serum, plasma, or urinefrom a subject is collected as a sample to be assayed according to thetype of the detection method used. Alternatively, total RNA preparedfrom such a body fluid by the method described above may be used, andvarious polynucleotides including cDNA prepared from the RNA may beused.

The kit or the device of the present invention is useful for thediagnosis of early pancreatic cancer or a pancreatic cancer precursorlesion or the detection of the presence or absence of early pancreaticcancer or a pancreatic cancer precursor lesion. Specifically, thedetection of early pancreatic cancer or a pancreatic cancer precursorlesion using the kit or the device can be performed by detecting invitro an expression level(s) of a gene(s) using the nucleic acidprobe(s) or the primer(s) contained in the kit or the device, in asample such as blood, serum, plasma, or urine from a subject suspectedof having early pancreatic cancer or a pancreatic cancer precursorlesion. The subject suspected of having early pancreatic cancer or apancreatic cancer precursor lesion can be evaluated as having earlypancreatic cancer or a pancreatic cancer precursor lesion when theexpression level(s) of a target miRNA marker(s) measured usingpolynucleotide(s) (including a variant(s), a fragment(s), and aderivative(s) thereof) consisting of a nucleotide sequence(s)represented by at least one (one or more) of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a complementary sequence(s) thereof, andoptionally a nucleotide sequence(s) represented by one or more of SEQ IDNOs: 84 to 226, 230 to 245, 247, and 249 or a complementary sequence(s)thereof, in the sample such as blood, serum, plasma, or urine of thesubject, has a statistically significant difference compared to anexpression level(s) thereof in the sample such as blood, serum, orplasma, or urine of a healthy subject.

The method of the present invention can be combined with a diagnosticimaging method such as abdominal ultrasonography, CT scanning,endoscopic retrograde cholangiopancreatography, or endoscopicultrasonography. The method of the present invention is capable ofspecifically detecting early pancreatic cancer or a pancreatic cancerprecursor lesion and can substantially discriminate early pancreaticcancer or a pancreatic cancer precursor lesion from the other cancers.Alternatively, these cancers can be discriminated therefrom bycombination with an additional diagnostic method such as the diagnosticimaging method as described above.

The method for detecting the absence of early pancreatic cancer or apancreatic cancer precursor lesion or the presence of early pancreaticcancer or a pancreatic cancer precursor lesion in a sample from asubject using the kit or the device of the present invention comprisescollecting a body fluid such as blood, serum, plasma, or urine of thesubject, and measuring the expression level(s) of the target gene(s) (orthe target nucleic acid(s)) contained therein using one or morepolynucleotides (including a variant(s), a fragment(s), or aderivative(s)) selected from the groups of polynucleotides of thepresent invention, to evaluate the presence or absence of earlypancreatic cancer or a pancreatic cancer precursor lesion or to detectearly pancreatic cancer or a pancreatic cancer precursor lesion. Themethod for detecting early pancreatic cancer or a pancreatic cancerprecursor lesion according to the present invention can also be used forevaluating or diagnosing, for example, the presence or absence ofamelioration of the disease or the degree of amelioration thereof in anearly pancreatic cancer or pancreatic cancer precursor lesion patient inthe case that a pancreatic cancer-related therapeutic drug known orunder development (non-limiting examples thereof include TS-1(three-component combination drug of tegafur/gimeracil/oteracilpotassium), Gemzar (gemcitabine hydrochloride), Tarceva (erlotinibhydrochloride), 5-FU (fluorouracil), levofolinate, irinotecan,oxaliplatin, Abraxane (nab-paclitaxel), and combinations thereof) isadministered to the patient for the purpose of treating or amelioratingthe disease.

The method of the present invention can comprise, for example, thefollowing steps (a), (b), and (c):

(a) a step of contacting in vitro a sample from a subject with apolynucleotide(s) contained in the kit or the device of the presentinvention;

(b) a step of measuring an expression level(s) of the target nucleicacid(s) in the sample using the polynucleotide(s) as a nucleic acidprobe(s) or primer(s); and

(c) a step of evaluating whether or not the subject has early pancreaticcancer or a pancreatic cancer precursor lesion (cells) on the basis ofthe measurement results in the step (b) to detect the presence orabsence of early pancreatic cancer or a pancreatic cancer precursorlesion (cells) in the subject.

In the step (a), blood, serum, or plasma can be used as a preferredsample.

In the step (b), the measurement of the expression level(s) can beperformed by a technique, for example, a hybridization technique such asa nucleic acid array method, a polynucleotide sequencing technique usinga sequencer or the like, or a quantitative amplification technique suchas quantitative RT-PCR.

In the step (c), the subject can be evaluated as having early pancreaticcancer or a pancreatic cancer precursor lesion on the basis of adiscriminant score prepared from the expression level(s) of the targetnucleic acid(s) in the sample from the subject and a discriminant(mentioned later) in the case that the expression level(s) of the targetnucleic acid(s) in the sample from the subject is statisticallysignificantly different from that in a sample(s) derived from a healthysubject(s) or benign pancreatic disease subject(s) (this expressionlevel(s) is also referred to as “reference” or “control”).

Specifically, the present invention provides a method for detectingearly pancreatic cancer or a pancreatic cancer precursor lesion in asubject, comprising: measuring an expression level(s) of a targetnucleic acid(s) in a sample of the subject using a nucleic acid(s)capable of specifically binding to at least one (one or more),preferably at least two, at least three, at least four, or at least fivepolynucleotides selected from the following miRNAs: miR-6784-5p,miR-1181, miR-671-5p, miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p,miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p,miR-1343-5p, miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p,miR-4728-5p, miR-652-5p, miR-4257, miR-6785-5p, miR-7110-5p,miR-6887-5p, miR-887-3p, miR-1228-5p, miR-5572, miR-6782-5p, miR-4298,miR-6786-5p, miR-5010-5p, miR-6087, miR-6765-5p, miR-6732-5p,miR-6787-5p, miR-6737-5p, miR-128-2-5p, miR-4270, miR-6861-5p,miR-6756-5p, miR-1229-5p, miR-6891-5p, miR-6848-5p, miR-1237-5p,miR-30c-1-3p, miR-1233-5p, miR-211-3p, miR-4758-5p, miR-614,miR-6746-5p, miR-1915-5p, miR-4688, miR-3917, miR-5787, miR-4632-5p,miR-6126, miR-135a-3p, miR-8063, miR-5698, miR-6089, miR-498,miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p, miR-6803-5p,miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p, miR-6131,miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p, miR-4448,miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447, miR-6869-5p,miR-6794-5p, miR-6511a-5p, miR-6824-5p, miR-6766-3p, miR-6511a-5p, andmiR-6749-5p; and evaluating in vitro whether or not the subject hasearly pancreatic cancer or a pancreatic cancer precursor lesion usingthe above-measured expression levels and control expression levels of ahealthy subject(s) measured in the same way as above, to detect thepresence or absence of early pancreatic cancer or a pancreatic cancerprecursor lesion in the subject.

As used herein, the term “evaluation” may be physician's judgement or isevaluation support based on results of in vitro examination withoutphysician's judgment.

As described above, in the method of the present invention,specifically, miR-6784-5p is hsa-miR-6784-5p, miR-1181 is hsa-miR-1181,miR-671-5p is hsa-miR-671-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4276is hsa-miR-4276, miR-1914-3p is hsa-miR-1914-3p, miR-149-3p ishsa-miR-149-3p, miR-937-5p is hsa-miR-937-5p, miR-4675 is hsa-miR-4675,miR-6795-5p is hsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090is hsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p ishsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p ishsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p ishsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p ishsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p ishsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p ishsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p ishsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p ishsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p ishsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 ishsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p ishsa-miR-6732-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p ishsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 ishsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p ishsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p ishsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p ishsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p ishsa-miR-1233-5p, miR-211-3p is hsa-miR-211-3p, miR-4758-5p ishsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p,miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 ishsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p,miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 ishsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089,miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b ishsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p ishsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p ishsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6752-5p ishsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 ishsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p ishsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920,miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 ishsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p,miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p ishsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p ishsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p ishsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, and miR-6749-5p ishsa-miR-6749-5p.

In the method of the present invention, specifically, the nucleicacid(s) (specifically, probe(s) or primer(s)) is selected from the groupconsisting of the following polynucleotides (a) to (e):

(a) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t, a variant thereof, a derivative thereof, or afragment thereof comprising 15 or more consecutive nucleotides;(b) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250;(c) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227to 229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(d) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t; and(e) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (a) to (d).

The nucleic acid(s) used in the method of the present invention canfurther comprise a nucleic acid(s) capable of specifically binding to atleast one (one or more) polynucleotides selected from the followingmiRNAs: miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125,miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689,miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p,miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p,miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p,miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p,miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p,miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718,miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p,miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a,miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449,miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p,miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p,miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p,miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p,miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p,miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513,miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p,miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975,miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p,miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505,miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476,miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141,miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648,miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-762,miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p,miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p,miR-4463, miR-4486, miR-4730, miR-4286, and miR-4739.

Specifically, miR-1908-5p is hsa-miR-1908-5p, miR-6729-5p ishsa-miR-6729-5p, miR-5195-3p is hsa-miR-5195-3p, miR-638 is hsa-miR-638,miR-6125 is hsa-miR-6125, miR-3178 is hsa-miR-3178, miR-3196 ishsa-miR-3196, miR-8069 is hsa-miR-8069, miR-4723-5p is hsa-miR-4723-5p,miR-4746-3p is hsa-miR-4746-3p, miR-4689 is hsa-miR-4689, miR-6816-5p ishsa-miR-6816-5p, miR-6757-5p is hsa-miR-6757-5p, miR-7109-5p ishsa-miR-7109-5p, miR-6724-5p is hsa-miR-6724-5p, miR-1225-3p ishsa-miR-1225-3p, miR-6875-5p is hsa-miR-6875-5p, miR-7108-5p ishsa-miR-7108-5p, miR-4508 is hsa-miR-4508, miR-6085 is hsa-miR-6085,miR-6779-5p is hsa-miR-6779-5p, miR-642a-3p is hsa-miR-642a-3p,miR-4695-5p is hsa-miR-4695-5p, miR-7847-3p is hsa-miR-7847-3p, miR-3197is hsa-miR-3197, miR-6769b-5p is hsa-miR-6769b-5p, miR-7641 ishsa-miR-7641, miR-187-5p is hsa-miR-187-5p, miR-3185 is hsa-miR-3185,miR-2861 is hsa-miR-2861, miR-3940-5p is hsa-miR-3940-5p, miR-1203 ishsa-miR-1203, miR-615-5p is hsa-miR-615-5p, miR-4787-5p ishsa-miR-4787-5p, miR-1343-3p is hsa-miR-1343-3p, miR-6813-5p ishsa-miR-6813-5p, miR-1225-5p is hsa-miR-1225-5p, miR-602 is hsa-miR-602,miR-4488 is hsa-miR-4488, miR-125a-3p is hsa-miR-125a-3p, miR-5100 ishsa-miR-5100, miR-4294 is hsa-miR-4294, miR-1231 is hsa-miR-1231,miR-6765-3p is hsa-miR-6765-3p, miR-4442 is hsa-miR-4442, miR-718 ishsa-miR-718, miR-6780b-5p is hsa-miR-6780b-5p, miR-6090 is hsa-miR-6090,miR-6845-5p is hsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 ishsa-miR-4467, miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271,miR-4673 is hsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 ishsa-miR-1469, miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a,miR-6791-5p is hsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p,miR-4433b-3p is hsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p,miR-4417 is hsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p ishsa-miR-4707-3p, miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p ishsa-miR-5585-3p, miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072,miR-296-5p is hsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 ishsa-miR-4454, miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290,miR-3622a-5p is hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p,miR-675-5p is hsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 ishsa-miR-4648, miR-1268b is hsa-miR-1268b, miR-6741-5p ishsa-miR-6741-5p, miR-6893-5p is hsa-miR-6893-5p, miR-3162-5p ishsa-miR-3162-5p, miR-642b-3p is hsa-miR-642b-3p, miR-4734 ishsa-miR-4734, miR-150-3p is hsa-miR-150-3p, miR-8089 is hsa-miR-8089,miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p is hsa-miR-7113-3p,miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p is hsa-miR-6799-5p,miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p is hsa-miR-92b-5p,miR-3679-5p is hsa-miR-3679-5p, miR-4792 is hsa-miR-4792, miR-3656 ishsa-miR-3656, miR-92a-2-5p is hsa-miR-92a-2-5p, miR-4466 ishsa-miR-4466, miR-4513 is hsa-miR-4513, miR-6781-5p is hsa-miR-6781-5p,miR-4649-5p is hsa-miR-4649-5p, miR-6775-5p is hsa-miR-6775-5p, miR-4651is hsa-miR-4651, miR-3195 is hsa-miR-3195, miR-6726-5p ishsa-miR-6726-5p, miR-6872-3p is hsa-miR-6872-3p, miR-371a-5p ishsa-miR-371a-5p, miR-6777-5p is hsa-miR-6777-5p, miR-6789-5p ishsa-miR-6789-5p, miR-7975 is hsa-miR-7975, miR-6821-5p ishsa-miR-6821-5p, miR-4534 is hsa-miR-4534, miR-619-5p is hsa-miR-619-5p,miR-7107-5p is hsa-miR-7107-5p, miR-1228-3p is hsa-miR-1228-3p,miR-6774-5p is hsa-miR-6774-5p, miR-6805-5p is hsa-miR-6805-5p,miR-23a-3p is hsa-miR-23a-3p, miR-4665-5p is hsa-miR-4665-5p, miR-4505is hsa-miR-4505, miR-4638-5p is hsa-miR-4638-5p, miR-24-3p ishsa-miR-24-3p, miR-3135b is hsa-miR-3135b, miR-4745-5p ishsa-miR-4745-5p, miR-128-1-5p is hsa-miR-128-1-5p, miR-4476 ishsa-miR-4476, miR-4687-3p is hsa-miR-4687-3p, miR-3665 is hsa-miR-3665,miR-6806-5p is hsa-miR-6806-5p, miR-3937 is hsa-miR-3937, miR-711 ishsa-miR-711, miR-3141 is hsa-miR-3141, miR-3188 is hsa-miR-3188,miR-4281 is hsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p, miR-6880-5p ishsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 is hsa-miR-3648,miR-6721-5p is hsa-miR-6721-5p, miR-4492 is hsa-miR-4492, miR-744-5p ishsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p ishsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p,miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 ishsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p,miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 ishsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076,miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 ishsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, andmiR-4739 is hsa-miR-4739.

Specifically, the nucleic acid(s) is further selected from the groupconsisting of the following polynucleotides (f) to (j):

(f) a polynucleotide consisting of a nucleotide sequence represented byany of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotidesequence derived from the nucleotide sequence by the replacement of uwith t, a variant thereof, a derivative thereof, or a fragment thereofcomprising 15 or more consecutive nucleotides;(g) a polynucleotide comprising a nucleotide sequence represented by anyof SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249;(h) a polynucleotide consisting of a nucleotide sequence complementaryto a nucleotide sequence represented by any of SEQ ID NOs: 84 to 226,230 to 245, 247, and 249 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides;(i) a polynucleotide comprising a nucleotide sequence complementary to anucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230 to245, 247, and 249 or a nucleotide sequence derived from the nucleotidesequence by the replacement of u with t; and(j) a polynucleotide hybridizing under stringent conditions to any ofthe polynucleotides (f) to (i).

Examples of the sample used in the method of the present invention caninclude samples prepared from living tissues (preferably pancreatictissues) or body fluids such as blood, serum, plasma, and urine fromsubjects. Specifically, for example, an RNA-containing sample preparedfrom the tissue, a polynucleotide-containing sample further preparedtherefrom, a body fluid such as blood, serum, plasma, or urine, aportion or the whole of a living tissue collected from the subject bybiopsy or the like, or a living tissue excised by surgery can be used,and the sample for measurement can be prepared therefrom.

The “subject” used herein refers to a mammal, for example, a primatesuch as a human or a monkey, a rodent such as a mouse or a rat, a petanimal such as a dog or a cat, an athletic animal such as a horse, andan animal that is kept in a zoo without any limitation, and ispreferably a human.

The steps of the method of the present invention can be changedaccording to the type of the sample to be assayed.

In the case of using RNA as an analyte, the detection of earlypancreatic cancer or a pancreatic cancer precursor lesion (cells) in asubject can comprise, for example, the following steps (a), (b), and(c):

(a) a step of binding RNA prepared from a sample from the subject orcomplementary polynucleotides (cDNAs) transcribed from the RNA to apolynucleotide(s) in the kit or the device of the present invention;

(b) a step of quantitatively or qualitatively measuring thesample-derived RNA or the cDNAs synthesized from the RNA, which is/arebound to the polynucleotide(s), by hybridization using thepolynucleotide(s) as a nucleic acid probe(s), by use of a sequencer forpolynucleotide sequencing, or by quantitative RT-PCR using thepolynucleotide(s) as a primer(s); and

(c) a step of evaluating in vitro whether or not the subject has earlypancreatic cancer or pancreatic cancer precursor lesion throughcomparison with a control on the basis of the measurement results of thestep (b), to detect the presence or absence of early pancreatic canceror a pancreatic cancer precursor lesion (or early pancreatic cancer- orpancreatic cancer precursor lesion-derived gene expression) in thesubject.

For example, various hybridization methods can be used for detecting,examining, evaluating, or diagnosing early pancreatic cancer or apancreatic cancer precursor lesion (or pancreatic cancer-derived geneexpression) in vitro according to the present invention. For example,Northern blot, Southern blot, RT-PCR, DNA chip analysis, in situhybridization, Northern hybridization, Southern hybridization, or apolynucleotide sequencing technique using a sequencer or the like can beused as such a hybridization method.

In the case of using the Northern blot, the presence or absence ofexpression of each gene or the expression level thereof in the RNA canbe detected or measured by use of the nucleic acid probe(s) that can beused in the present invention. Specific examples thereof can include amethod which comprises labeling the nucleic acid probe (or acomplementary strand) with a radioisotope (³²P, ³³P, ³⁵S, etc.), afluorescent material, or the like, hybridizing the labeled product withthe living tissue-derived RNA from a subject, which is transferred to anylon membrane or the like according to a routine method, and thendetecting and measuring a signal derived from the label (radioisotope orfluorescent material) on the formed DNA/RNA duplex using a radiationdetector (examples thereof can include BAS-1800 II (Fujifilm Corp.,Japan)) or a fluorescence detector (examples thereof can include STORM865 (GE Healthcare Japan Corp.)).

In the case of using the quantitative RT-PCR, the presence or absence ofexpression of each gene or the expression level thereof in the RNA canbe detected or measured by use of the primer that can be used in thepresent invention. Specific examples thereof can include a method whichcomprises preparing cDNAs from the living tissue-derived RNA of asubject according to a routine method, hybridizing a pair of primers(consisting of a plus strand and a reverse strand binding to the cDNA)prepared from the composition for detection of the present inventionwith the cDNA and performing PCR according to a routine method such thatthe region of each target gene can be amplified with the cDNA as atemplate, and thereby detecting the obtained double-stranded DNA. Themethod for detecting the double-stranded DNA can include a method ofperforming the PCR using the primers labeled in advance with aradioisotope or a fluorescent material, a method of electrophoresing thePCR product on an agarose gel and staining the double-stranded DNA withethidium bromide or the like for detection, and a method of transferringthe produced double-stranded DNA to a nylon membrane or the likeaccording to a routine method and hybridizing the double-stranded DNA toa labeled nucleic acid probe for detection.

In the case of using the sequencer, the presence or absence ofexpression of each gene or the expression level thereof in the RNA canbe detected or measured from the number of reads by use of the primerthat can be used in the present invention. Specific examples thereof caninclude a method which comprises preparing cDNAs from the livingtissue-derived RNA of a subject according to a routine method,hybridizing a pair of primers (consisting of a plus strand and a reversestrand binding to the cDNA) prepared from the composition for detectionof the present invention with the cDNA and performing PCR according to aroutine method such that the region of each target gene can be amplifiedwith the cDNA as a template, and detecting or measuring the amplifiedDNA using a sequencer such as HiSeq 2500 (Illumina, Inc.) or Ion Proton®System (Thermo Fisher Scientific Inc.). Another specific example thereofcan include a method which comprises detecting or measuring the livingtissue-derived RNA of a subject using PacBio RS II (Pacific Biosciencesof California, Inc.) without PCR amplification.

In the case of using the nucleic acid array technique (or analysis), anRNA chip or a DNA chip on which the composition for detection of thepresent invention is attached as nucleic acid probes (single-stranded ordouble-stranded) to a substrate (solid phase) is used. Regions havingthe attached nucleic acid probes are referred to as probe spots, andregions having no attached nucleic acid probe are referred to as blankspots. A substrate on which a group of genes are immobilized isgenerally called a nucleic acid chip, a nucleic acid array, amicroarray, or the like. The DNA or RNA array includes a DNA or RNAmacroarray and a DNA or RNA microarray. In the present specification,the term “chip” includes these arrays. 3D-Gene® Human miRNA Oligo chip(Toray Industries, Inc.) can be used as the DNA chip, though the DNAchip is not limited thereto.

Examples of the measurement using the DNA chip can include, but are notlimited to, a method of detecting and measuring a signal derived fromthe label of the composition for detection using an image detector(examples thereof can include Typhoon 9410 (GE Healthcare) and 3D-Gene®scanner (Toray Industries, Inc.)).

The “stringent conditions” used herein are, as mentioned above,conditions under which a nucleic acid probe hybridizes to its targetsequence to a detectably larger extent (e.g., a measurement value equalto or larger than “(a mean of background measurement values)+(a standarderror of the background measurement values)×2”) than that for othersequences.

The stringent conditions are defined by hybridization and subsequentwashing. Examples of the hybridization conditions include, but notlimited to, 30° C. to 60° C. for 1 to 24 hours in a solution containingSSC, a surfactant, formamide, dextran sulfate, a blocking agent(s), etc.In this context, 1×SSC is an aqueous solution (pH 7.0) containing 150 mMsodium chloride and 15 mM sodium citrate. The surfactant includes, forexample, SDS (sodium dodecyl sulfate), Triton, or Tween. Thehybridization conditions more preferably comprise 3-10×SSC and 0.1-1%SDS. Furthermore, examples of the conditions for the washing, followingthe hybridization, which is another condition to define the stringentconditions, can include conditions comprising sequential washing at 30°C. in a solution containing 0.5×SSC and 0.1% SDS, at 30° C. in asolution containing 0.2×SSC and 0.1% SDS, and at 30° C. in a 0.05×SSCsolution. It is desirable that the complementary strand should maintainits hybridized state with a target plus strand even during washing undersuch conditions. Specifically, examples of such a complementary strandcan include a strand consisting of a nucleotide sequence in a completelycomplementary relationship with the nucleotide sequence of the targetplus strand, and a strand consisting of a nucleotide sequence having atleast 80%, preferably at least 85%, more preferably at least 90% or atleast 95%, for example, at least 98% or at least 99% identity to thestrand.

Other examples of the “stringent conditions” for the hybridization aredescribed in, for example, Sambrook, J. & Russel, D., Molecular Cloning,A LABORATORY MANUAL, Cold Spring Harbor Laboratory Press, published onJan. 15, 2001, Vol. 1, 7.42 to 7.45 and Vol. 2, 8.9 to 8.17, and can beused in the present invention.

Examples of the conditions for carrying out PCR using polynucleotidefragments in the kit of the present invention as primers includetreatment for approximately 15 seconds to 1 minute at a Tm value+5-10°C., wherein the Tm value is calculated from the sequences of theprimers, using a PCR buffer having composition such as 10 mM Tris-HCL(pH 8.3), 50 mM KCL, and 1 to 2 mM MgCl₂. Examples of the method forcalculating such a Tm value include Tm value=2×(the number of adenineresidues+the number of thymine residues)+4×(the number of guanineresidues+the number of cytosine residues).

In the case of using the quantitative RT-PCR, a commercially availablekit for measurement specially designed for quantitatively measuringmiRNA, such as TaqMan® MicroRNA Assays (Life Technologies Corp.),LNA®-based MicroRNA PCR (Exiqon), or Ncode® miRNA qRT-PCT kit(Invitrogen Corp.) may be used.

For the calculation of gene expression levels, statistical processingdescribed in, for example, Statistical analysis of gene expressionmicroarray data (Speed T., Chapman and Hall/CRC), and A beginner's guideMicroarray gene expression data analysis (Causton H. C. et al.,Blackwell publishing) can be used in the present invention, though thecalculation method is not limited thereto. For example, twice,preferably 3 times, more preferably 6 times the standard deviation ofthe measurement values of the blank spots are added to the averagemeasurement value of the blank spots on the DNA chip, and probe spotshaving a signal value equal to or larger than the resulting value can bedefined as detection spots. Furthermore, the average measurement valueof the blank spots can be considered as a background and can besubtracted from the measurement values of the probe spots to determinethe resulting value as gene expression levels. A missing value for agene expression level can be excluded from the analyte, preferablyreplaced with the smallest value of the gene expression level in eachDNA chip, or more preferably replaced with a value obtained bysubtracting 0.1 from a logarithmic value of the smallest value of thegene expression level. In order to exclude low-signal genes, only a genehaving a gene expression level of 2⁶, preferably 2⁸, more preferably 2¹⁰or larger in 20% or more, preferably 50% or more, more preferably 80% ormore of the number of measurement samples can be selected as theanalyte. Examples of the normalization of the gene expression levelinclude, but are not limited to, global normalization and quantilenormalization (Bolstad, B. M. et al., 2003, Bioinformatics, Vol. 19, p.185-193).

The present invention also provides a method for detecting (or assistingin the detection of) early pancreatic cancer or a pancreatic cancerprecursor lesion in a subject, comprising measuring expression levels oftarget genes in a sample from the subject using the polynucleotides, thekit, or the device (e.g., chip) for diagnosis of the present invention,or a combination thereof, and assigning the expression levels of thetarget genes in the sample from the subject to a discriminant(discriminant function) to evaluate the presence or absence of earlypancreatic cancer or a pancreatic cancer precursor lesion, wherein thediscriminant is prepared with gene expression levels in a sample from asubject (or a patient) known to have early pancreatic cancer or apancreatic cancer precursor lesion and gene expression levels in asample from a healthy subject as supervising samples and is capable ofdiscriminating an early pancreatic cancer or pancreatic cancer precursorlesion patient from a healthy subject.

The present invention further provides the method comprising: a firststep of measuring in vitro expression levels of target genes in aplurality of samples from subjects known to have early pancreatic canceror a pancreatic cancer precursor lesion and/or to have neither earlypancreatic cancer nor a pancreatic cancer precursor lesion, using thepolynucleotides, the kit, or the device (e.g., chip) for diagnosis ofthe present invention, or a combination thereof; a second step ofpreparing a discriminant with the measurement values of the expressionlevels of the target genes obtained in the first step as supervisingsamples; a third step of measuring in vitro expression levels of thetarget genes in a sample derived from a subject in the same way as inthe first step; and a fourth step of assigning the measurement values ofthe expression levels of the target genes obtained in the third step tothe discriminant obtained in the second step, and determining orevaluating the presence or absence of early pancreatic cancer or apancreatic cancer precursor lesion in the subject on the basis of theresults obtained from the discriminant, wherein the target genes can bedetected using the polynucleotides, the polynucleotides contained in thekit or the device (e.g., chip), variants thereof, or fragments thereof.

As used herein, the discriminant can be prepared by use of anydiscriminant analysis method that can prepare a discriminant fordiscriminating an early pancreatic cancer or pancreatic cancer precursorlesion patient from a healthy subject, for example, Fisher'sdiscriminant analysis, nonlinear discriminant analysis based onMahalanobis' distance, neural network, or Support Vector Machine (SVM),though the method is not limited thereto.

When a clustering boundary is a straight line or a hyperplane, thelinear discriminant analysis is a method for determining the belongingof a cluster using Formula 1 as a discriminant. In Formula 1, xrepresents an explanatory variable, w represents a coefficient of theexplanatory variable, and w₀ represents a constant term.

$\begin{matrix}{{f(x)} = {w_{0} + {\sum\limits_{i = 1}^{n}\; {w_{i}x_{i}}}}} & {{Formula}\mspace{14mu} 1}\end{matrix}$

Values obtained from the discriminant are referred to as discriminantscores. The measurement values of a newly offered dataset can beassigned as explanatory variables to the discriminant to determineclusters by the signs (+ or −) of the discriminant scores.

The Fisher's discriminant analysis, one type of linear discriminantanalysis, is a dimensionality reduction method for selecting a dimensionsuitable for discriminating classes, and constructs a highlydiscriminating synthetic variable by focusing on the variance of thesynthetic variables and minimizing the variance of data having the samelabel (Venables, W. N. et al., Modern Applied Statistics with S. Fourthedition. Springer, 2002). In the Fisher's discriminant analysis,projection direction w is determined so as to maximize Formula 2. Inthis formula, t represents an average input, n_(g) represents the numberof data belonging to class g, and g represents an average input of thedata belonging to class g. The numerator and the denominator are theinterclass variance and the intraclass variance, respectively, when eachdata is projected in the direction of the vector w. Discriminantcoefficient w_(i) is determined by maximizing this ratio (TakafumiKanamori et al., “Pattern Recognition”, Kyoritsu Shuppan Co., Ltd.,(Tokyo, Japan) (2009); and Richard O. et al., Pattern ClassificationSecond Edition., Wiley-Interscience, 2000).

$\begin{matrix}{{{J(w)} = \frac{\sum\limits_{g = 1}^{G}\; {{n_{g}\left( {{w^{T}\mu_{g}} - {w^{T}\mu}} \right)}\left( {{w^{T}\mu_{g}} - {w^{T}\mu}} \right)^{T}}}{{\sum\limits_{g = 1}^{G}\; {\sum\limits_{{i:y_{i}} = g}{\left( {{w^{T}x_{i}} - {w^{T}\mu_{g}}} \right)\left( {{w^{T}x_{i}} - {w^{T}\mu_{g}}} \right)}}}\;}}{{{\text{subject to}\mspace{14mu} \mu} = {\sum\limits_{i = 1}^{n}\; \frac{x_{i}}{n}}},{\mu_{g} = {\sum\limits_{{i:u_{i}} = g}^{n}\; \frac{x_{i}}{n_{g}}}}}} & {{Formula}\mspace{14mu} 2}\end{matrix}$

The Mahalanobis' distance is calculated according to Formula 3 inconsideration of data correlation and can be used as nonlineardiscriminant analysis for determining a cluster to which a data pointbelongs, based on the smallest Mahalanobis' distance between the datapoint and each cluster. In Formula 3, μ represents a central vector ofeach cluster, and S⁻¹ represents an inverse matrix of thevariance-covariance matrix of the cluster. The central vector iscalculated from explanatory variable x, and an average vector, a medianvalue vector, or the like can be used.

$\begin{matrix}{{D\left( {x,\mu} \right)} = \left\{ {\left( {x - \mu} \right)^{t}{S^{- 1}\left( {x - \mu} \right)}} \right\}^{\frac{1}{2}}} & {{Formula}\mspace{14mu} 3}\end{matrix}$

SVM is a discriminant analysis method devised by V. Vapnik (The Natureof Statistical Leaning Theory, Springer, 1995). Particular data pointsof a dataset having known classes are defined as explanatory variables,and classes are defined as objective variables. A boundary plane calledhyperplane for correctly classifying the dataset into the known classesis determined, and a discriminant for data classification is determinedusing the boundary plane. Then, the measurement values of a newlyoffered dataset can be assigned as explanatory variables to thediscriminant to determine classes. In this respect, the result of thediscriminant analysis may be classes, may be a probability of beingclassified into correct classes, or may be the distance from thehyperplane. In SVM, a method of nonlinearly converting a feature vectorto a high dimension and performing linear discriminant analysis in thespace is known as a method for tackling nonlinear problems. Anexpression in which an inner product of two factors in a nonlinearlymapped space is expressed only by inputs in their original spaces iscalled kernel. Examples of the kernel can include a linear kernel, a RBF(Radial Basis Function) kernel, and a Gaussian kernel. While highlydimensional mapping is performed according to the kernel, the optimumdiscriminant, i.e., a discriminant, can be actually constructed by merecalculation according to the kernel, which avoids calculating featuresin the mapped space (e.g., Hideki Aso et al., Frontier of StatisticalScience 6 “Statistics of pattern recognition and learning—New conceptsand approaches”, Iwanami Shoten, Publishers, (Tokyo, Japan) (2004);Nello Cristianini et al., Introduction to SVM, Kyoritsu Shuppan Co.,Ltd., (Tokyo, Japan) (2008)).

C-support vector classification (C-SVC), one type of SVM, comprisespreparing a hyperplane by supervision according to a dataset with theexplanatory variables of two groups and classifying an unknown datasetinto either of the groups (C. Cortes et al., 1995, Machine Learning,Vol. 20, p. 273-297).

Exemplary calculation of the C-SVC discriminant that can be used in themethod of the present invention will be given below. First, all subjectsare divided into two groups, i.e., an early pancreatic cancer orpancreatic cancer precursor lesion patient group and a healthy subjectgroup. For example, pancreatic tissue examination can be used for areference under which each subject is confirmed either as an earlypancreatic cancer or pancreatic cancer precursor lesion patient or as ahealthy subject.

Next, a dataset consisting of comprehensive gene expression levels ofserum-derived samples of the two divided groups (hereinafter, thisdataset is referred to as a training cohort) is prepared, and a C-SVCdiscriminant is determined by using genes found to differ clearly intheir gene expression levels between the two groups as explanatoryvariables and this grouping as objective variables (e.g., −1 and +1). Anoptimizing objective function is represented by Formula 4 wherein erepresents all input vectors, y represents an objective variable, arepresents a Lagrange multiplier vector, Q represents a positivedefinite matrix, and C represents a parameter for adjusting constrainedconditions.

$\begin{matrix}{{{\min\limits_{a}{\frac{1}{2}a^{T}{Qa}}} - {e^{T}a}}{{{\text{subject to}\mspace{14mu} y^{T}a} = 0},{0 \leq a_{i} \leq C},{i = 1},\ldots \mspace{11mu},l,}} & {{Formula}\mspace{14mu} 4}\end{matrix}$

Formula 5 is a finally obtained discriminant, and a group to which thedata point belongs to can be determined on the basis of the sign of avalue obtained according to the discriminant. In this formula, xrepresents a support vector, y represents a label indicating thebelonging of a group, a represents the corresponding coefficient, brepresents a constant term, and K represents a kernel function.

$\begin{matrix}{{f(x)} = {{sgn}\left( {{\sum\limits_{i = 1}^{l}\; {y_{i}a_{i}{K\left( {x_{i},x} \right)}}} + b} \right)}} & {{Formula}\mspace{14mu} 5}\end{matrix}$

For example, a RBF kernel defined by Formula 6 can be used as the kernelfunction. In this formula, x represents a support vector, and γrepresents a kernel parameter for adjusting the complexity of thehyperplane.

K(x _(i) ,x _(j))=exp(−r∥x _(i) −x _(j)∥²), r<0  Formula 6

In addition, an approach such as neural network, k-nearest neighboralgorithms, decision trees, or logistic regression analysis can beselected as a method for determining or evaluating the presence and/orabsence of an early pancreatic cancer or pancreatic cancer precursorlesion in a subject, or for evaluating the expression level thereof bycomparison with a control derived from a healthy subject.

The method of the present invention can comprise, for example, thefollowing steps (a), (b), and (c):

(a) a step of measuring an expression level(s) of a target gene(s) insamples already known to be derived from early pancreatic cancer orpancreatic cancer precursor lesion patients and to be derived fromhealthy subjects or subjects having neither early pancreatic cancer nora pancreatic cancer precursor lesion, using the polynucleotide(s), thekit, or the device (e.g., DNA chip) for detection according to thepresent invention;

(b) a step of preparing the discriminants of Formulas 1 to 3, 5, and 6described above from the measurement values of the expression levelmeasured in the step (a); and

(c) a step of measuring an expression level(s) of the target gene(s) ina sample derived from a subject using the polynucleotide(s), the kit, orthe device (e.g., DNA chip) for diagnosis (detection) according to thepresent invention, assigning the obtained measurement value(s) to thediscriminants prepared in the step (b), and determining or evaluatingthe presence or absence of early pancreatic cancer or a pancreaticcancer precursor lesion in the subject, or evaluating early pancreaticcancer- or pancreatic cancer precursor lesion-derived expression levelsby comparison with a healthy subject-derived control, on the basis ofthe obtained results.

In this context, in the discriminants of Formulas 1 to 3, 5, and 6, xrepresents an explanatory variable and includes a value obtained bymeasuring a polynucleotide(s) selected from the polynucleotides or thelike described in Section 2 above, or any fragment thereof.Specifically, the explanatory variable for discriminating an earlypancreatic cancer or pancreatic cancer precursor lesion patient from ahealthy subject according to the present invention is a gene expressionlevel(s) selected from, for example, the following expression levels (1)to (2):

(1) a gene expression level(s) in the serum of an early pancreaticcancer or pancreatic cancer precursor lesion patient and a healthysubject measured by any of RNAs or DNAs comprising 15 or moreconsecutive nucleotides in a nucleotide sequence represented by any ofSEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or a complementarysequence thereof, or nucleotides derived from the nucleotides by thereplacement of u with t;

(2) a gene expression level(s) in the serum of an early pancreaticcancer or pancreatic cancer precursor lesion patient and a healthysubject measured by any of RNAs or DNAs comprising 15 or moreconsecutive nucleotides in a nucleotide sequence represented by any ofSEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a complementarysequence thereof, or nucleotides derived from the nucleotides by thereplacement of u with t; and

As described above, for the method for determining or evaluating whetheror not a subject has early pancreatic cancer or a pancreatic cancerprecursor lesion as to a sample derived from the subject, thepreparation of a discriminant requires a discriminant prepared from atraining cohort. For enhancing the discrimination accuracy of thediscriminant, it is necessary to use genes having clear difference intheir expression level between two groups consisting of an earlypancreatic cancer or pancreatic cancer precursor lesion patient groupand a healthy subject group in the training cohort when preparing thediscriminant.

Each gene that is used for an explanatory variable in a discriminant ispreferably determined as follows. First, comprehensive gene expressionlevels of an early pancreatic cancer or pancreatic cancer precursorlesion patient group and comprehensive gene expression levels of ahealthy subject group, both of which are in a training cohort, are usedas a dataset, and the degree of difference in the expression level ofeach gene between the two groups is determined through the use of, forexample, the P value of t test, which is parametric analysis, or the Pvalue of Mann-Whitney's U test or Wilcoxon test, which is nonparametricanalysis.

The degree of difference in the expression level can be considered asbeing statistically significant when the critical rate (significancelevel) as the P value obtained by the test is smaller than, for example,5%, 1%, or 0.01%.

In order to correct an increased probability of type I error attributedto the repetition of a test, a method known in the art, for example,Bonferroni or Holm method, can be used for the correction (e.g., YasushiNagata et al., “Basics of statistical multiple comparison methods”,Scientist Press Co., Ltd. (Tokyo, Japan) (2007)). As an example of theBonferroni correction, for example, the P value obtained by a test ismultiplied by the number of repetitions of the test, i.e., the number ofgenes used in the analysis, and the obtained value can be compared witha desired significance level to reduce a probability of causing type Ierror in the whole test.

Instead of the test, the absolute value (fold change) of an expressionratio of a median value of each gene expression level between geneexpression levels of an early pancreatic cancer or pancreatic cancerprecursor lesion patient group and gene expression levels of a healthysubject group may be calculated to select a gene that is used for anexplanatory variable in a discriminant. Alternatively, ROC curves may beprepared using gene expression levels of an early pancreatic cancer orpancreatic cancer precursor lesion patient group and a healthy subjectgroup, and a gene that is used for an explanatory variable in adiscriminant can be selected on the basis of an AUROC value.

Next, a discriminant that can be calculated by various methods describedabove is prepared using any number of genes having large difference intheir gene expression levels determined here. Examples of the method forconstructing a discriminant that produces the largest discriminationaccuracy include a method of constructing a discriminant in everycombination of genes that satisfy the significance level for P value,and a method of repetitively evaluating the genes for use in thepreparation of a discriminant while increasing the number of genes oneby one in a descending order of difference in gene expression level(Furey T S. et al., 2000, Bioinformatics., Vol. 16, p. 906-14). A geneexpression level of another independent early pancreatic cancer orpancreatic cancer precursor lesion patient or healthy subject isassigned as an explanatory variable to this discriminant to calculatediscrimination results of the group to which this independent earlypancreatic cancer or pancreatic cancer precursor lesion patient orhealthy subject belongs. Specifically, the identified gene set fordiagnosis and the discriminant constructed using the gene set fordiagnosis can be evaluated with an independent sample cohort to identifya more universal gene set for diagnosis capable of detecting earlypancreatic cancer or a pancreatic cancer precursor lesion and a moreuniversal method for discriminating early pancreatic cancer or apancreatic cancer precursor lesion.

Split-sample method is preferably used for evaluating the discriminationperformance (generalization) of the discriminant. Specifically, adataset is divided into a training cohort and a validation cohort, andgene selection by a statistical test and discriminant preparation areperformed using the training cohort. Accuracy, sensitivity, andspecificity are calculated using a result of discriminating a validationcohort according to the discriminant, and a true group to which thevalidation cohort belongs, to evaluate the discrimination performance ofthe discriminant. On the other hand, instead of dividing a dataset, thegene selection by a statistical test and discriminant preparation may beperformed using all of samples, and accuracy, sensitivity, andspecificity can be calculated by discriminating a newly prepared samplewith the discriminant for evaluation of the discrimination performanceof the discriminant.

The present invention provides polynucleotides for disease diagnosisuseful in the diagnosis and treatment of early pancreatic cancer or apancreatic cancer precursor lesion, a method for detecting earlypancreatic cancer or a pancreatic cancer precursor lesion using thepolynucleotide(s), and a kit and a device for the detection of earlypancreatic cancer or a pancreatic cancer precursor lesion, comprisingthe polynucleotide(s). Particularly, in order to select a gene(s) fordiagnosis and prepare a discriminant so as to exhibit accuracy beyondthe early pancreatic cancer or pancreatic cancer precursor lesiondiagnosis methods using the existing tumor markers CEA and CA19-9, agene set for diagnosis and a discriminant for the method of the presentinvention can be constructed, which exhibit accuracy beyond CEA andCA19-9, for example, by comparing expressed genes in serum from apatient confirmed to be negative using CEA and CA19-9 but finally foundto have early pancreatic cancer or a pancreatic cancer precursor lesionby detailed examination such as computed tomography using a contrastmedium, with genes expressed in serum from a patient having no earlypancreatic cancer or pancreatic cancer precursor lesion.

For example, the gene set for diagnosis is determined as any combinationselected from one or two or more of the polynucleotides based on anucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, or a complementarysequence thereof as described above; and optionally one or two or moreof the polynucleotides based on a nucleotide sequence represented by anyof SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotidesequence derived from the nucleotide sequence by the replacement of uwith t, or a complementary sequence thereof; and optionally one or twoor more of the polynucleotides based on a nucleotide sequencerepresented by any of SEQ ID NOs: 227 to 245 or a nucleotide sequencederived from the nucleotide sequence by the replacement of u with t, ora complementary sequence thereof. Further, a discriminant is constructedusing expression levels of the gene set for diagnosis in samples fromclass I early pancreatic cancer or pancreatic cancer precursor lesionpatients as a result of tissue diagnosis and samples from class IIhealthy subjects and/or other cancers and/or benign diseases as a resultof tissue diagnosis. As a result, the presence or absence of earlypancreatic cancer or a pancreatic cancer precursor lesion in a subjectfrom which an unknown sample is derived can be determined with 100%accuracy at the maximum by measuring expression levels of the gene setfor diagnosis in the unknown sample.

EXAMPLES

Hereinafter, the present invention will be described furtherspecifically with reference to Examples below. However, the scope of thepresent invention is not intended to be limited by these Examples.

Reference Example 1

<Collection of Samples of Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion Patient and Healthy Subject>

Sera were collected using VENOJECT II vacuum blood collecting tubeVP-AS109K60 (Terumo Corp., Japan) from each of 21 pancreatic cancerprecursor lesion patients (4 cases with IPMA low grade, 5 cases withIPMA high grade, and 12 cases with IPMC) confirmed to have no cancer inorgans, 31 early pancreatic cancer patients (9 cases with stage IIA and22 cases with stage IIB) confirmed to have no cancer in organs otherthan the pancreas, and 123 healthy subjects after obtainment of informedconsent, and used as a training cohort. Likewise, sera were collectedusing VENOJECT II vacuum blood collecting tube VP-AS109K60 (TerumoCorp.) from each of 12 pancreatic cancer precursor lesion patients (3cases with IPMA low grade, 3 cases with IPMA high grade, and 6 caseswith IPMC) confirmed to have no cancer in organs, 13 early pancreaticcancer patients (3 cases with stage IIA and 10 cases with stage IIB)confirmed to have no cancer in organs other than the pancreas, and 61healthy subjects after obtainment of informed consent, and used as avalidation cohort.

<Extraction of Total RNA>

Total RNA was obtained using a reagent for RNA extraction in 3D-Gene®RNA extraction reagent from liquid sample kit (Toray Industries, Inc.,Japan) according to the protocol provided by the manufacturer from 300μL of the serum sample obtained from each of 261 persons in total of 33pancreatic cancer precursor lesion patients, 184 healthy subjects, and44 early pancreatic cancer patients included in the training cohort andthe validation cohort.

<Measurement of Gene Expression Level>

miRNAs in the total RNA obtained from sera of each of the 261 persons intotal of the 33 pancreatic cancer precursor lesion patients, the 184healthy subjects, and the 44 early pancreatic cancer patients includedin the training cohort and the validation cohort were fluorescentlylabeled using 3D-Gene® miRNA Labeling kit (Toray Industries, Inc.)according to the protocol (ver 2.20) provided by the manufacturer. Theoligo DNA chip used was 3D-Gene® Human miRNA Oligo chip (TorayIndustries, Inc.) with attached probes having sequences complementary to2,555 miRNAs among the miRNAs registered in miRBase Release 20.Hybridization under stringent conditions and washing following thehybridization were performed according to the protocol provided by themanufacturer. The DNA chip was scanned using 3D-Gene® scanner (TorayIndustries, Inc.) to obtain images. Fluorescence intensity was digitizedusing 3D-Gene® Extraction (Toray Industries, Inc.). The digitizedfluorescence intensity was converted to a logarithmic value having abase of 2 and used as a gene expression level, from which a blank valuewas subtracted. A missing value was replaced with a value obtained bysubtracting 0.1 from a logarithmic value of the smallest value of thegene expression level in each DNA chip. As a result, the comprehensivegene expression levels of the miRNAs in the sera were obtained from eachof the 261 persons in total of the 33 pancreatic cancer precursor lesionpatients, the 184 healthy subjects, and the 46 early pancreatic cancerpatients. Calculation and statistical analysis using the digitized geneexpression levels of the miRNAs were carried out using R language 3.0.2(R Development Core Team (2013). R: A language and environment forstatistical computing. R Foundation for Statistical Computing, URLhttp://www.R-project.org/.) and MASS package 7.3-30 (Venables, W. N. &Ripley, B. D. (2002) Modern Applied Statistics with S. Fourth Edition.Springer, New York. ISBN 0-387-95457-0).

Reference Example 2

<Collection of Samples of Other Cancers and Benign Diseases>

Sera were collected using VENOJECT II vacuum blood collecting tubeVP-AS109K60 (Terumo Corp.) from each of 61 advanced pancreatic cancerpatients, 66 bile duct cancer patients, 31 colorectal cancer patients,32 stomach cancer patients, 34 esophageal cancer patients, 38 livercancer patients, and 15 benign pancreatic disease patients confirmed tohave no cancer in other organs after obtainment of informed consent.Also, data on 51 breast cancer patients, 35 prostate cancer patients,and 26 benign prostatic disease patients was extracted from the data setunder Accession No. GSE73002 of a gene expression information databaseGene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/). Thesesamples were used as a training cohort together with the samples of 21pancreatic cancer precursor lesion patients (4 cases with IPMA lowgrade, 5 cases with IPMA high grade, and 12 cases with IPMC), 31 earlypancreatic cancer patients (8 cases with stage HA and 22 cases withstage IIB), and 128 healthy subjects of Reference Example 1. Likewise,sera were collected using VENOJECT II vacuum blood collecting tubeVP-AS109K60 (Terumo Corp.) from each of 39 advanced pancreatic cancerpatients, 32 bile duct cancer patients, 19 colorectal cancer patients,18 stomach cancer patients, 16 esophageal cancer patients, 14 livercancer patients, and 9 benign pancreatic disease patients confirmed tohave no cancer in other organs after obtainment of informed consent.Also, data on 23 breast cancer patients, 17 prostate cancer patients,and 15 benign prostatic disease patients was extracted from the datasetunder Accession No. GSE73002 of a gene expression information databaseGene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/). Thesesamples were used as a validation cohort together with the samples of 12pancreatic cancer precursor lesion patients (3 cases with IPMA lowgrade, 3 cases with IPMA high grade, and 6 cases with IPMC), 13 earlypancreatic cancer patients (3 cases with stage HA and 10 cases withstage IIB), and 56 healthy subjects of Reference Example 1. Subsequentextraction of total RNA and measurement and analysis of gene expressionlevels were conducted in the same way as in Reference Example 1.

Example 1

<Selection of Gene Markers Using Samples of the Training Cohort, andMethod for Evaluating Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion Discriminant Performance of the Single Gene MarkerUsing the Validation Cohort>

In this Example, a gene marker for discriminating an early pancreaticcancer or pancreatic cancer precursor lesion patient as a positivecontrol group from a healthy subject as a negative control group wasselected from the training cohort and studied in samples of thevalidation cohort independent of the training cohort.

Specifically, first, the miRNA expression levels of the training cohortand the validation cohort obtained in the preceding Reference Exampleswere combined and normalized by global normalization.

Next, genes for diagnosis were selected using the training cohort. Here,in order to acquire diagnostic markers with higher reliability, onlygenes having the expression level of 2⁶ or higher in 50% or more of thesamples in either of the early pancreatic cancer or pancreatic cancerprecursor lesion patient group of the training cohort or the healthysubject group of the training cohort were selected. In order to furtheracquire statistically significant genes for discriminating an earlypancreatic cancer or pancreatic cancer precursor lesion patient groupfrom a healthy subject group, the P value obtained by two-tailed t-testassuming equal variance as to each gene expression level was correctedby the Bonferroni method, and genes that satisfied p<0.01 were acquiredas gene markers for use in explanatory variables of a discriminant anddescribed in Table 2.

In this way, hsa-miR-6784-5p, hsa-miR-1181, hsa-miR-671-5p,hsa-miR-6857-5p, hsa-miR-4276, hsa-miR-1914-3p, hsa-miR-149-3p,hsa-miR-937-5p, hsa-miR-4675, hsa-miR-6795-5p, hsa-miR-4731-5p,hsa-miR-5090, hsa-miR-3620-5p, hsa-miR-1343-5p, hsa-miR-6717-5p,hsa-miR-6825-5p, hsa-miR-6738-5p, hsa-miR-6769a-5p, hsa-miR-4728-5p,hsa-miR-652-5p, hsa-miR-4257, hsa-miR-6785-5p, hsa-miR-7110-5p,hsa-miR-6887-5p, hsa-miR-887-3p, hsa-miR-1228-5p, hsa-miR-5572,hsa-miR-6782-5p, hsa-miR-4298, hsa-miR-6786-5p, hsa-miR-5010-5p,hsa-miR-6087, hsa-miR-6765-5p, hsa-miR-6732-5p, hsa-miR-6787-5p,hsa-miR-6737-5p, hsa-miR-128-2-5p, hsa-miR-4270, hsa-miR-6861-5p,hsa-miR-6756-5p, hsa-miR-1229-5p, hsa-miR-6891-5p, hsa-miR-6848-5p,hsa-miR-1237-5p, hsa-miR-30c-1-3p, hsa-miR-1233-5p, hsa-miR-211-3p,hsa-miR-4758-5p, hsa-miR-614, hsa-miR-6746-5p, hsa-miR-1915-5p,hsa-miR-4688, hsa-miR-3917, hsa-miR-5787, hsa-miR-4632-5p, hsa-miR-6126,hsa-miR-135a-3p, hsa-miR-8063, hsa-miR-5698, hsa-miR-6089, hsa-miR-498,hsa-miR-296-3p, hsa-miR-4419b, hsa-miR-6802-5p, hsa-miR-6829-5p,hsa-miR-6803-5p, hsa-miR-1199-5p, hsa-miR-6840-3p, hsa-miR-6752-5p,hsa-miR-6798-5p, hsa-miR-6131, hsa-miR-4667-5p, hsa-miR-6510-5p,hsa-miR-4690-5p, hsa-miR-920, hsa-miR-23b-3p, hsa-miR-4448,hsa-miR-2110, hsa-miR-4706, hsa-miR-7845-5p, hsa-miR-6808-5p,hsa-miR-4447, hsa-miR-6869-5p, hsa-miR-1908-5p, hsa-miR-6729-5p,hsa-miR-5195-3p, hsa-miR-638, hsa-miR-6125, hsa-miR-3178, hsa-miR-3196,hsa-miR-8069, hsa-miR-4723-5p, hsa-miR-4746-3p, hsa-miR-4689,hsa-miR-6816-5p, hsa-miR-6757-5p, hsa-miR-7109-5p, hsa-miR-6724-5p,hsa-miR-1225-3p, hsa-miR-6875-5p, hsa-miR-7108-5p, hsa-miR-4508,hsa-miR-6085, hsa-miR-6779-5p, hsa-miR-642a-3p, hsa-miR-4695-5p,hsa-miR-7847-3p, hsa-miR-3197, hsa-miR-6769b-5p, hsa-miR-7641,hsa-miR-187-5p, hsa-miR-3185, hsa-miR-2861, hsa-miR-3940-5p,hsa-miR-1203, hsa-miR-615-5p, hsa-miR-4787-5p, hsa-miR-1343-3p,hsa-miR-6813-5p, hsa-miR-1225-5p, hsa-miR-602, hsa-miR-4488,hsa-miR-125a-3p, hsa-miR-5100, hsa-miR-4294, hsa-miR-1231,hsa-miR-6765-3p, hsa-miR-4442, hsa-miR-718, hsa-miR-6780b-5p,hsa-miR-6090, hsa-miR-6845-5p, hsa-miR-4741, hsa-miR-4467,hsa-miR-4707-5p, hsa-miR-4271, hsa-miR-4673, hsa-miR-3184-5p,hsa-miR-1469, hsa-miR-4640-5p, hsa-miR-663a, hsa-miR-6791-5p,hsa-miR-6826-5p, hsa-miR-4433b-3p, hsa-miR-1915-3p, hsa-miR-4417,hsa-miR-4449, hsa-miR-4707-3p, hsa-miR-3180-3p, hsa-miR-5585-3p,hsa-miR-1268a, hsa-miR-8072, hsa-miR-296-5p, hsa-miR-204-3p,hsa-miR-4454, hsa-miR-6722-3p, hsa-miR-1290, hsa-miR-3622a-5p,hsa-miR-939-5p, hsa-miR-675-5p, hsa-miR-3131, hsa-miR-4648,hsa-miR-1268b, hsa-miR-6741-5p, hsa-miR-6893-5p, hsa-miR-3162-5p,hsa-miR-642b-3p, hsa-miR-4734, hsa-miR-150-3p, hsa-miR-8089,hsa-miR-6805-3p, hsa-miR-7113-3p, hsa-miR-6850-5p, hsa-miR-6799-5p,hsa-miR-6768-5p, hsa-miR-92b-5p, hsa-miR-3679-5p, hsa-miR-4792,hsa-miR-3656, hsa-miR-92a-2-5p, hsa-miR-4466, hsa-miR-4513,hsa-miR-6781-5p, hsa-miR-4649-5p, hsa-miR-6775-5p, hsa-miR-4651,hsa-miR-3195, hsa-miR-6726-5p, hsa-miR-6872-3p, hsa-miR-371a-5p,hsa-miR-6777-5p, hsa-miR-6789-5p, hsa-miR-7975, hsa-miR-6821-5p,hsa-miR-4534, hsa-miR-619-5p, hsa-miR-7107-5p, hsa-miR-1228-3p,hsa-miR-6774-5p, hsa-miR-6805-5p, hsa-miR-23a-3p, hsa-miR-4665-5p,hsa-miR-4505, hsa-miR-4638-5p, hsa-miR-24-3p, hsa-miR-3135b,hsa-miR-4745-5p, hsa-miR-128-1-5p, hsa-miR-4476, hsa-miR-4687-3p,hsa-miR-3665, hsa-miR-6806-5p, hsa-miR-3937, hsa-miR-711, hsa-miR-3141,hsa-miR-3188, hsa-miR-4281, hsa-miR-5196-5p, hsa-miR-6880-5p,hsa-miR-3960, hsa-miR-3648, hsa-miR-6721-5p, hsa-miR-4492,hsa-miR-744-5p, hsa-miR-7704, and hsa-miR-4749-5p genes, and thenucleotide sequences of SEQ ID NOs: 1 to 226 related thereto wereidentified.

A discriminant for determining the presence or absence of earlypancreatic cancer or a pancreatic cancer precursor lesion was furtherprepared by Fisher's discriminant analysis with the expression levels ofthese genes as indicators. Specifically, any newly found expressionlevel measurement values of polynucleotide consisting of a nucleotidesequence represented by any of SEQ ID NOs: 1 to 83 among the 226 genesselected in the training cohort was input to Formula 2 above to preparea discriminant. Calculated accuracy, sensitivity, and specificity areshown in Table 3. In this respect, a discriminant coefficient and aconstant term are shown in Table 4.

Next, accuracy, sensitivity, and specificity in the validation cohortwere calculated using the discriminant thus prepared, and thediscriminant performance of the selected polynucleotides was validatedusing independent samples (Table 3). For example, the discriminant scoreobtained by use of Fisher's discriminant analysis from the expressionlevel measurement value of the nucleotide sequence represented by SEQ IDNO: 1 was compared between the pancreatic cancer precursor lesionpatients (21 persons) or the early pancreatic cancer patients (31persons) and the healthy subjects in the training cohort. As a result,the discriminant score in the training cohort was found to besignificantly higher in the early pancreatic cancer or pancreatic cancerprecursor lesion group than in the healthy subject group (see the leftdiagram of FIG. 2). These results were also reproducible in thevalidation cohort (see the right diagram of FIG. 2). Likewise, theresults obtained about the other polynucleotides shown in SEQ ID NOs: 1to 226 showed that the gene expression level measurement values weresignificantly lower (decrease) or higher (increase) in the earlypancreatic cancer or pancreatic cancer precursor lesion patient groupthan in the healthy subject group (Table 2). These results were able tobe validated in the validation cohort. For example, as for thisnucleotide sequence represented by SEQ ID NO: 1, the number of correctlyor incorrectly identified samples in the detection of early pancreaticcancer or a pancreatic cancer precursor lesion in the validation cohortwas calculated using the threshold (0) that was set in the trainingcohort for discriminating the two groups. As a result, 22 truepositives, 52 true negatives, 9 false positives, and 4 false negativeswere obtained. From these values, 85.1% accuracy, 84.6% sensitivity, and85.2% specificity were obtained as the detection performance. In thisway, the detection performance was calculated as to all of thepolynucleotides shown in SEQ ID NOs: 1 to 83, and described in Table 3.Among the polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NOs: 1 to 83 shown in Table 2, for example, 26polynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 2, 3, 18, 12, 20, 1, 15, 50, 63, 72, 5, 24, 10, 52, 9, 11,19, 39, 61, 7, 17, 22, 26, 74, 21, and 28 exhibited sensitivity of 100%,92.3%, 92.3%, 76.9%, 80.8%, 84.6%, 76.9%, 84.6%, 73.1%, 80.8%, 88.5%,88.5%, 88.5%, 73.1%, 73.1%, 76.9%, 61.5%, 65.4%, 84.6%, 92.3%, 73.1%,61.5%, 76.9%, 73.1%, 80.8%, and 92.3%, respectively, in the validationcohort (Table 3). As seen from Comparative Examples mentioned later, theexisting markers CEA and CA19-9 had sensitivity of 20% and 68%,respectively, in the validation cohort (Table 5-2), demonstrating that,for example, the 26 polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 2, 3, 18, 12, 20, 1, 15, 50, 63,72, 5, 24, 10, 52, 9, 11, 19, 39, 61, 7, 17, 22, 26, 74, 21, and 28 candiscriminate, each alone, early pancreatic cancer or a pancreatic cancerprecursor lesion in the validation cohort with sensitivity beyond orequivalent to CA19-9.

Example 2

<Method a for Evaluating Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion Discriminant Performance by Combination of Plurality ofGene Markers Using Samples in the Validation Cohort>

In this Example, a method for evaluating early pancreatic cancer or apancreatic cancer precursor lesion discriminant performance by acombination of the gene markers selected in Example 1 was studied.

Specifically, Fisher's discriminant analysis was conducted as to 15,272combinations of two expression level measurement values comprising atleast one or more of the expression level measurement values of thenewly found polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NOs: 1 to 83 among the polynucleotides consistingof the nucleotide sequences represented by SEQ ID NOs: 1 to 226 selectedin Example 1, to construct a discriminant for determining the presenceor absence of early pancreatic cancer or a pancreatic cancer precursorlesion. Next, accuracy, sensitivity, and specificity in the validationcohort were calculated using the discriminant thus prepared, and thediscriminant performance of the selected polynucleotides was validatedusing independent samples. For example, the expression level measurementvalues of the nucleotide sequences represented by SEQ ID NO: 1 and SEQID NO: 2 were compared between the pancreatic cancer precursor lesionpatients (21 persons) or the early pancreatic cancer patients (31persons) and the healthy subjects (123 persons) in the training cohort.As a result, a scatter diagram that significantly separated theexpression level measurement values of the early pancreatic cancer orpancreatic cancer precursor lesion patient group from those of thehealthy subject group was obtained in the training cohort. These resultswere also reproducible in the validation cohort. Likewise, a scatterdiagram that significantly separated the gene expression levelmeasurement values of the early pancreatic cancer or pancreatic cancerprecursor lesion patient group from those of the healthy subject groupwas also obtained as to the other combinations of two expression levelmeasurement values comprising at least one of the expression levelmeasurement values of the newly found polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 1 to 83 among thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 1 to 226. These results were able to be validated in thevalidation cohort. For example, as for these nucleotide sequencesrepresented by SEQ ID NO: 1 and SEQ ID NO: 2, the number of correctly orincorrectly identified samples in the detection of early pancreaticcancer or a pancreatic cancer precursor lesion was calculated using thethreshold (0=1.90×hsa-miR-6784-5p+1.72×hsa-miR-1181−34.50) that was setin the training cohort for discriminating the two groups. As a result,52 true positives, 107 true negatives, 16 false positives, and 1 falsenegative were obtained in the training cohort. From these values, 90.3%accuracy, 98.1% sensitivity, and 87% specificity were obtained as thedetection performance (see the left diagram of FIG. 3). These resultswere also reproducible in the validation cohort (see the right diagramof FIG. 3). In this way, the detection performance was calculated forall of the combinations of two expression level measurement valuescomprising at least one of the expression level measurement values ofthe newly found polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NOs: 1 to 83 among the polynucleotides consistingof the nucleotide sequences represented by SEQ ID NOs: 1 to 226. Amongthem, 225 combinations comprising the expression level measurement valueof the polynucleotide consisting of the nucleotide sequence representedby SEQ ID NO: 1, and the detection performance thereof are described inTable 6 as an example. In Table 6, “SEQ ID NO” indicates thecombinations of a plurality of polynucleotides used by SEQ ID NO (thesame applies to the tables mentioned later herein). For example, thecombinations of the expression level measurement values of thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NO: 1 and SEQ ID NO: 2, SEQ ID NO: 1 and SEQ ID NO: 3, SEQ ID NO:1 and SEQ ID NO: 4, and SEQ ID NO: 1 and SEQ ID NO: 5 showed sensitivityof 92.3%, 88.5%, 84.6%, 88.5%, and 84.6%, respectively, in thevalidation cohort (Table 6). Further, the combinations of twopolynucleotides consisting of nucleotide sequences other than SEQ ID NO:1 are shown in Table 7 as an example. For example, the combinations ofSEQ ID NOs: 2 and 18, SEQ ID NOs: 2 and 53, SEQ ID NOs: 2 and 20, SEQ IDNOs: 2 and 3, SEQ ID NOs: 2 and 50, SEQ ID NOs: 85 and 3, SEQ ID NOs: 84and 3, SEQ ID NOs: 90 and 3, SEQ ID NOs: 87 and 3, SEQ ID NOs: 90 and18, SEQ ID NOs: 87 and 18, SEQ ID NOs: 89 and 18, SEQ ID NOs: 84 and 18,SEQ ID NOs: 85 and 12, SEQ ID NOs: 85 and 20, SEQ ID NOs: 84 and 20, SEQID NOs: 90 and 20, SEQ ID NOs: 87 and 20, SEQ ID NOs: 87 and 15, SEQ IDNOs: 85 and 15, SEQ ID NOs: 2 and 15, SEQ ID NOs: 85 and 50, SEQ ID NOs:87 and 50, SEQ ID NOs: 84 and 50, SEQ ID NOs: 106 and 50, SEQ ID NOs: 90and 50, SEQ ID NOs: 2 and 63, SEQ ID NOs: 85 and 63, SEQ ID NOs: 90 and63, SEQ ID NOs: 87 and 63, SEQ ID NOs: 84 and 72, SEQ ID NOs: 85 and 72,SEQ ID NOs: 88 and 72, SEQ ID NOs: 87 and 72, SEQ ID NOs: 85 and 5, SEQID NOs: 87 and 5, SEQ ID NOs: 84 and 5, SEQ ID NOs: 85 and 10, SEQ IDNOs: 90 and 10, SEQ ID NOs: 85 and 52, SEQ ID NOs: 88 and 52, SEQ IDNOs: 87 and 52, SEQ ID NOs: 98 and 52, SEQ ID NOs: 84 and 52, SEQ IDNOs: 87 and 9, SEQ ID NOs: 85 and 9, SEQ ID NOs: 117 and 9, SEQ ID NOs:88 and 9, SEQ ID NOs: 87 and 11, SEQ ID NOs: 85 and 11, SEQ ID NOs: 102and 11, SEQ ID NOs: 84 and 11, SEQ ID NOs: 85 and 19, SEQ ID NOs: 87 and19, SEQ ID NOs: 88 and 19, SEQ ID NOs: 89 and 19, SEQ ID NOs: 87 and 39,SEQ ID NOs: 85 and 39, SEQ ID NOs: 2 and 39, SEQ ID NOs: 87 and 61, SEQID NOs: 85 and 61, SEQ ID NOs: 88 and 61, SEQ ID NOs: 88 and 7, SEQ IDNOs: 85 and 7, SEQ ID NOs: 87 and 7, SEQ ID NOs: 91 and 7, SEQ ID NOs:85 and 17, SEQ ID NOs: 87 and 17, SEQ ID NOs: 85 and 22, SEQ ID NOs: 87and 22, SEQ ID NOs: 117 and 22, SEQ ID NOs: 85 and 26, SEQ ID NOs: 87and 26, SEQ ID NOs: 84 and 26, SEQ ID NOs: 85 and 74, SEQ ID NOs: 2 and74, SEQ ID NOs: 87 and 74, SEQ ID NOs: 84 and 74, SEQ ID NOs: 88 and 74,SEQ ID NOs: 85 and 28, and SEQ ID NOs: 84 and 28 as specificcombinations of two polynucleotides showed sensitivity of 95% or higherto discriminate early pancreatic cancer or pancreatic cancer precursorlesion patients from healthy subjects in both of the training cohort andthe validation cohort. In this way, the 14,079 combinations of theexpression level measurement values of the polynucleotides havingsensitivity beyond the existing marker CA19-9 (68% from Table 5-2) wereobtained in the validation cohort. All of the nucleotide sequences 1 to226 described in Table 2 obtained in Example 1 were employed at leastonce in these combinations. These results demonstrated that thecombinations of two expression level measurement values comprising atleast one of the expression level measurement values of thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 1 to 226 detect early pancreatic cancer or a pancreaticcancer precursor lesion with sensitivity beyond CA19-9 in the validationcohort.

Thus, markers capable of detecting early pancreatic cancer or apancreatic cancer precursor lesion with excellent sensitivity areobtained even if 3, 4, 5, 6, 7, 8, 9, 10 or more of the expression levelmeasurement values of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 1 to 226 are combined. For example,the polynucleotides consisting of the nucleotide sequences representedby SEQ ID NOs: 1 to 226 selected in Example 1 were ranked in thedescending order of their P values which indicate statisticalsignificance, and detection performance was calculated usingcombinations of one or more miRNAs to which the miRNAs were added one byone from the top to the bottom according to the rank. As a result, thesensitivity in the validation cohort was 69.2% for 2 miRNAs, 80.8% for 5miRNAs, 92.3% for 10 miRNAs, 96.2% for 20 miRNAs, 100% for 100 miRNAs,and 100% for 226 miRNAs. These values of the sensitivity were higherthan the sensitivity of the existing tumor marker in blood,demonstrating that even combinations of a plurality of the miRNAs canserve as excellent markers for the detection of early pancreatic canceror a pancreatic cancer precursor lesion. In this context, thecombinations of a plurality of the miRNAs are not limited to thecombinations of the miRNAs added in the order of statisticallysignificant difference as described above, and any combination of aplurality of the miRNAs can be used in the detection of early pancreaticcancer or a pancreatic cancer precursor lesion.

From these results, it can be concluded that all of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 1 to226 serve as excellent diagnostic markers.

Tables 2, 3, 4, 5, 6, and 7 mentioned above are as follows.

TABLE 2 Change in expression level in early pancreatic cancer P valueafter and pancreatic cancer SEQ ID Bonferroni precursor lesion patientNO: Gene name correction relative to healthy subject 1 hsa-miR-6784-5p8.01E−38 Increase 2 hsa-miR-1181 1.56E−37 Increase 3 hsa-miR-671-5p4.06E−32 Decrease 4 hsa-miR-6857-5p 1.70E−31 Increase 5 hsa-miR-42762.59E−29 Increase 6 hsa-miR-1914-3p 5.13E−28 Decrease 7 hsa-miR-149-3p6.76E−25 Decrease 8 hsa-miR-937-5p 1.08E−24 Decrease 9 hsa-miR-46758.93E−24 Decrease 10 hsa-miR-6795-5p 3.80E−23 Decrease 11hsa-miR-4731-5p 5.78E−23 Decrease 12 hsa-miR-5090 9.07E−23 Decrease 13hsa-miR-3620-5p 5.97E−22 Increase 14 hsa-miR-1343-5p 3.10E−21 Increase15 hsa-miR-6717-5p 1.26E−20 Decrease 16 hsa-miR-6825-5p 3.53E−20Increase 17 hsa-miR-6738-5p 5.73E−20 Decrease 18 hsa-miR-6769a-5p6.03E−20 Decrease 19 hsa-miR-4728-5p 6.45E−20 Decrease 20 hsa-miR-652-5p6.72E−20 Decrease 21 hsa-miR-4257 9.04E−20 Decrease 22 hsa-miR-6785-5p1.42E−19 Decrease 23 hsa-miR-7110-5p 2.12E−19 Increase 24hsa-miR-6887-5p 2.20E−19 Decrease 25 hsa-miR-887-3p 3.36E−19 Increase 26hsa-miR-1228-5p 8.56E−19 Increase 27 hsa-miR-5572 3.16E−18 Increase 28hsa-miR-6782-5p 2.24E−17 Decrease 29 hsa-miR-4298 2.85E−17 Decrease 30hsa-miR-6786-5p 1.52E−16 Increase 31 hsa-miR-5010-5p 2.17E−16 Decrease32 hsa-miR-6087 9.02E−16 Increase 33 hsa-miR-6765-5p 2.35E−15 Increase34 hsa-miR-6732-5p 4.15E−15 Increase 35 hsa-miR-6787-5p 9.05E−15Decrease 36 hsa-miR-6737-5p 9.97E−15 Increase 37 hsa-miR-128-2-5p1.76E−14 Decrease 38 hsa-miR-4270 2.27E−14 Decrease 39 hsa-miR-6861-5p2.90E−14 Decrease 40 hsa-miR-6756-5p 8.32E−14 Decrease 41hsa-miR-1229-5p 4.69E−13 Decrease 42 hsa-miR-6891-5p 7.35E−13 Decrease43 hsa-miR-6848-5p 1.26E−12 Increase 44 hsa-miR-1237-5p 9.08E−12Increase 45 hsa-miR-30c-1-3p 1.04E−11 Decrease 46 hsa-miR-1233-5p2.45E−11 Decrease 47 hsa-miR-211-3p 3.35E−11 Decrease 48 hsa-miR-4758-5p4.39E−11 Decrease 49 hsa-miR-614 5.53E−11 Decrease 50 hsa-miR-6746-5p9.72E−11 Decrease 51 hsa-miR-1915-5p 1.53E−10 Decrease 52 hsa-miR-46881.67E−10 Decrease 53 hsa-miR-3917 2.52E−10 Decrease 54 hsa-miR-57872.64E−10 Increase 55 hsa-miR-4632-5p 2.94E−10 Increase 56 hsa-miR-61263.79E−10 Increase 57 hsa-miR-135a-3p 7.42E−10 Increase 58 hsa-miR-80631.29E−09 Decrease 59 hsa-miR-5698 3.21E−09 Decrease 60 hsa-miR-60892.31E−08 Increase 61 hsa-miR-498 2.38E−08 Decrease 62 hsa-miR-296-3p5.37E−08 Decrease 63 hsa-miR-4419b 1.02E−07 Decrease 64 hsa-miR-6802-5p1.69E−07 Decrease 65 hsa-miR-6829-5p 2.31E−07 Decrease 66hsa-miR-6803-5p 3.54E−07 Increase 67 hsa-miR-1199-5p 5.49E−07 Decrease68 hsa-miR-6840-3p 7.30E−07 Decrease 69 hsa-miR-6752-5p 3.97E−06Increase 70 hsa-miR-6798-5p 1.85E−05 Increase 71 hsa-miR-6131 4.80E−05Decrease 72 hsa-miR-4667-5p 9.09E−05 Decrease 73 hsa-miR-6510-5p1.04E−04 Decrease 74 hsa-miR-4690-5p 1.22E−04 Decrease 75 hsa-miR-9201.49E−04 Decrease 76 hsa-miR-23b-3p 1.85E−04 Decrease 77 hsa-miR-44482.38E−04 Increase 78 hsa-miR-2110 3.99E−04 Decrease 79 hsa-miR-47065.83E−04 Decrease 80 hsa-miR-7845-5p 2.34E−03 Increase 81hsa-miR-6808-5p 4.82E−03 Decrease 82 hsa-miR-4447 5.38E−03 Decrease 83hsa-miR-6869-5p 6.71E−03 Increase 84 hsa-miR-1908-5p 3.48E−50 Increase85 hsa-miR-6729-5p 1.20E−47 Increase 86 hsa-miR-5195-3p 4.85E−45Decrease 87 hsa-miR-638 6.56E−44 Increase 88 hsa-miR-6125 2.97E−42Increase 89 hsa-miR-3178 3.76E−41 Increase 90 hsa-miR-3196 2.70E−39Increase 91 hsa-miR-8069 3.80E−36 Increase 92 hsa-miR-4723-5p 3.97E−36Decrease 93 hsa-miR-4746-3p 1.24E−35 Increase 94 hsa-miR-4689 2.84E−35Decrease 95 hsa-miR-6816-5p 3.48E−35 Increase 96 hsa-miR-6757-5p1.20E−34 Decrease 97 hsa-miR-7109-5p 1.21E−34 Decrease 98hsa-miR-6724-5p 2.96E−34 Increase 99 hsa-miR-1225-3p 2.03E−33 Increase100 hsa-miR-6875-5p 5.61E−33 Increase 101 hsa-miR-7108-5p 4.48E−32Increase 102 hsa-miR-4508 1.03E−31 Increase 103 hsa-miR-6085 7.30E−30Decrease 104 hsa-miR-6779-5p 7.94E−30 Decrease 105 hsa-miR-642a-3p1.28E−28 Decrease 106 hsa-miR-4695-5p 1.37E−28 Increase 107hsa-miR-7847-3p 1.49E−28 Decrease 108 hsa-miR-3197 1.08E−27 Increase 109hsa-miR-6769b-5p 1.82E−27 Decrease 110 hsa-miR-7641 3.73E−27 Decrease111 hsa-miR-187-5p 1.45E−26 Decrease 112 hsa-miR-3185 1.98E−26 Increase113 hsa-miR-2861 4.70E−26 Increase 114 hsa-miR-3940-5p 2.68E−25 Increase115 hsa-miR-1203 3.13E−25 Increase 116 hsa-miR-615-5p 9.78E−25 Decrease117 hsa-miR-4787-5p 4.84E−24 Increase 118 hsa-miR-1343-3p 7.76E−24Decrease 119 hsa-miR-6813-5p 9.50E−24 Decrease 120 hsa-miR-1225-5p2.32E−22 Increase 121 hsa-miR-602 3.00E−22 Increase 122 hsa-miR-44885.30E−22 Increase 123 hsa-miR-125a-3p 1.08E−21 Decrease 124 hsa-miR-51001.58E−21 Increase 125 hsa-miR-4294 2.49E−21 Decrease 126 hsa-miR-12313.00E−21 Increase 127 hsa-miR-6765-3p 5.05E−21 Decrease 128 hsa-miR-44428.24E−21 Decrease 129 hsa-miR-718 1.55E−20 Increase 130 hsa-miR-6780b-5p3.10E−20 Increase 131 hsa-miR-6090 1.16E−19 Increase 132 hsa-miR-6845-5p1.52E−19 Increase 133 hsa-miR-4741 1.58E−19 Increase 134 hsa-miR-44673.00E−19 Increase 135 hsa-miR-4707-5p 3.49E−19 Increase 136 hsa-miR-42711.16E−18 Decrease 137 hsa-miR-4673 1.20E−18 Increase 138 hsa-miR-3184-5p1.69E−18 Increase 139 hsa-miR-1469 1.98E−18 Increase 140 hsa-miR-4640-5p2.13E−18 Increase 141 hsa-miR-663a 3.70E−18 Increase 142 hsa-miR-6791-5p9.89E−18 Increase 143 hsa-miR-6826-5p 5.46E−17 Decrease 144hsa-miR-4433b-3p 1.49E−16 Increase 145 hsa-miR-1915-3p 1.61E−16 Increase146 hsa-miR-4417 3.24E−16 Increase 147 hsa-miR-4449 6.68E−16 Increase148 hsa-miR-4707-3p 9.83E−16 Increase 149 hsa-miR-3180-3p 1.06E−15Increase 150 hsa-miR-5585-3p 3.68E−15 Increase 151 hsa-miR-1268a4.67E−15 Increase 152 hsa-miR-8072 8.29E−15 Increase 153 hsa-miR-296-5p1.70E−14 Decrease 154 hsa-miR-204-3p 2.59E−14 Decrease 155 hsa-miR-44542.97E−14 Decrease 156 hsa-miR-6722-3p 3.47E−14 Increase 157 hsa-miR-12905.12E−14 Increase 158 hsa-miR-3622a-5p 5.86E−14 Decrease 159hsa-miR-939-5p 9.18E−14 Increase 160 hsa-miR-675-5p 1.25E−13 Decrease161 hsa-miR-3131 1.26E−13 Decrease 162 hsa-miR-4648 1.93E−13 Increase163 hsa-miR-1268b 2.06E−13 Increase 164 hsa-miR-6741-5p 2.25E−13Decrease 165 hsa-miR-6893-5p 5.59E−13 Decrease 166 hsa-miR-3162-5p1.01E−12 Decrease 167 hsa-miR-642b-3p 1.51E−12 Decrease 168 hsa-miR-47347.47E−12 Increase 169 hsa-miR-150-3p 3.02E−11 Decrease 170 hsa-miR-80893.88E−11 Decrease 171 hsa-miR-6805-3p 4.65E−11 Increase 172hsa-miR-7113-3p 6.07E−11 Increase 173 hsa-miR-6850-5p 1.45E−10 Increase174 hsa-miR-6799-5p 2.02E−10 Decrease 175 hsa-miR-6768-5p 2.10E−10Increase 176 hsa-miR-92b-5p 2.27E−10 Increase 177 hsa-miR-3679-5p3.05E−10 Increase 178 hsa-miR-4792 4.13E−10 Increase 179 hsa-miR-36568.02E−10 Increase 180 hsa-miR-92a-2-5p 9.84E−10 Increase 181hsa-miR-4466 1.70E−09 Increase 182 hsa-miR-4513 1.79E−09 Decrease 183hsa-miR-6781-5p 2.02E−09 Increase 184 hsa-miR-4649-5p 3.34E−09 Decrease185 hsa-miR-6775-5p 7.94E−09 Decrease 186 hsa-miR-4651 2.08E−08 Decrease187 hsa-miR-3195 4.19E−08 Increase 188 hsa-miR-6726-5p 4.45E−08 Decrease189 hsa-miR-6872-3p 7.91E−08 Decrease 190 hsa-miR-371a-5p 1.32E−07Decrease 191 hsa-miR-6777-5p 2.82E−07 Decrease 192 hsa-miR-6789-5p5.95E−07 Increase 193 hsa-miR-7975 1.00E−06 Decrease 194 hsa-miR-6821-5p1.36E−06 Decrease 195 hsa-miR-4534 5.94E−06 Decrease 196 hsa-miR-619-5p6.51E−06 Increase 197 hsa-miR-7107-5p 1.06E−05 Decrease 198hsa-miR-1228-3p 1.07E−05 Increase 199 hsa-miR-6774-5p 1.08E−05 Decrease200 hsa-miR-6805-5p 1.10E−05 Increase 201 hsa-miR-23a-3p 2.26E−05Decrease 202 hsa-miR-4665-5p 3.25E−05 Decrease 203 hsa-miR-4505 7.17E−05Increase 204 hsa-miR-4638-5p 7.59E−05 Decrease 205 hsa-miR-24-3p8.75E−05 Decrease 206 hsa-miR-3135b 1.20E−04 Decrease 207hsa-miR-4745-5p 1.24E−04 Increase 208 hsa-miR-128-1-5p 1.45E−04 Increase209 hsa-miR-4476 1.81E−04 Decrease 210 hsa-miR-4687-3p 1.94E−04 Decrease211 hsa-miR-3665 2.61E−04 Increase 212 hsa-miR-6806-5p 3.17E−04 Decrease213 hsa-miR-3937 3.45E−04 Increase 214 hsa-miR-711 6.28E−04 Increase 215hsa-miR-3141 6.80E−04 Increase 216 hsa-miR-3188 6.88E−04 Increase 217hsa-miR-4281 9.34E−04 Decrease 218 hsa-miR-5196-5p 1.33E−03 Decrease 219hsa-miR-6880-5p 1.48E−03 Increase 220 hsa-miR-3960 2.60E−03 Increase 221hsa-miR-3648 3.23E−03 Increase 222 hsa-miR-6721-5p 3.69E−03 Increase 223hsa-miR-4492 4.89E−03 Increase 224 hsa-miR-744-5p 8.59E−03 Increase 225hsa-miR-7704 8.95E−03 Increase 226 hsa-miR-4749-5p 8.96E−03 Increase

TABLE 3 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 1 89.8 96.2 87 85.1 84.6 85.2 2 89.8 96.2 87 89.7 100 85.2 387.5 86.8 87.8 94.3 92.3 95.1 4 88.1 96.2 84.6 90.8 92.3 90.2 5 88.694.3 86.2 85.1 88.5 83.6 6 88.6 86.8 89.4 89.7 84.6 91.8 7 84.1 86.882.9 92 92.3 91.8 8 85.8 79.2 88.6 89.7 88.5 90.2 9 84.1 84.9 83.7 79.373.1 82 10 85.8 84.9 86.2 86.2 88.5 85.2 11 84.7 88.7 82.9 81.6 76.983.6 12 86.9 92.5 84.6 83.9 76.9 86.9 13 85.8 94.3 82.1 83.9 88.5 82 1484.7 79.2 87 74.7 61.5 80.3 15 84.1 84.9 83.7 80.5 76.9 82 16 83 83 82.978.2 73.1 80.3 17 83 77.4 85.4 80.5 73.1 83.6 18 85.2 90.6 82.9 85.192.3 82 19 81.2 83 80.5 79.3 61.5 86.9 20 84.7 84.9 84.6 82.8 80.8 83.621 86.9 80.8 89.4 85.1 80.8 86.9 22 81.8 73.6 85.4 74.7 61.5 80.3 2379.5 83 78 74.7 76.9 73.8 24 86.9 81.1 89.4 80.5 88.5 77 25 84.1 94.379.7 81.6 88.5 78.7 26 79.5 81.1 78.9 78.2 76.9 78.7 27 80.1 86.8 77.274.7 73.1 75.4 28 83 81.1 83.7 89.7 92.3 88.5 29 78.4 75.5 79.7 79.161.5 86.7 30 78.4 73.6 80.5 83.9 80.8 85.2 31 79.5 83 78 86.2 96.2 82 3279 94.3 72.4 83.9 100 77 33 80.1 81.1 79.7 77 80.8 75.4 34 77.8 86.8 7481.6 80.8 82 35 79.5 84.9 77.2 82.8 88.5 80.3 36 81.2 84.9 79.7 79.376.9 80.3 37 77.3 71.7 79.7 75.9 61.5 82 38 75.6 79.2 74 73.6 73.1 73.839 76.7 75.5 77.2 70.1 65.4 72.1 40 75 75.5 74.8 74.7 80.8 72.1 41 73.971.7 74.8 83.9 92.3 80.3 42 79.5 69.8 83.7 75.9 73.1 77 43 80.7 81.180.5 83.9 69.2 90.2 44 75.6 79.2 74 74.7 80.8 72.1 45 77.8 75.5 78.978.2 69.2 82 46 75.6 77.4 74.8 67.8 61.5 70.5 47 76.1 86.8 71.5 72.465.4 75.4 48 75 77.4 74 69 69.2 68.9 49 74.4 71.7 75.6 69 57.7 73.8 5079 83 77.2 79.3 84.6 77 51 77.8 77.4 78 77 76.9 77 52 73.9 81.1 70.774.7 73.1 75.4 53 71 81.1 66.7 71.3 69.2 72.1 54 73.9 67.9 76.4 79.373.1 82 55 78.4 62.3 85.4 74.7 61.5 80.3 56 73.9 67.9 76.4 72.4 73.172.1 57 77.3 86.8 73.2 74.7 80.8 72.1 58 73.9 73.6 74 69 57.7 73.8 5971.6 81.1 67.5 78.2 73.1 80.3 60 76.1 71.7 78 77 69.2 80.3 61 72.7 75.571.5 78.2 84.6 75.4 62 69.9 71.7 69.1 73.6 73.1 73.8 63 74.4 86.8 69.172.4 73.1 72.1 64 71.6 75.5 69.9 66.7 80.8 60.7 65 69.9 67.9 70.7 67.873.1 65.6 66 67.6 62.3 69.9 73.6 69.2 75.4 67 72.2 73.6 71.5 66.7 69.265.6 68 72.2 71.7 72.4 63.2 57.7 65.6 69 68.2 79.2 63.4 72.4 80.8 68.970 68.8 75.5 65.9 62.1 65.4 60.7 71 71 62.3 74.8 73.3 68 75.4 72 67 75.563.4 70.1 80.8 65.6 73 68.8 62.3 71.5 70.1 69.2 70.5 74 68.8 69.8 68.366.7 73.1 63.9 75 69.3 66 70.7 74.7 80.8 72.1 76 72.7 69.8 74 73.6 57.780.3 77 64.8 73.6 61 58.6 73.1 52.5 78 65.9 66 65.9 73.6 73.1 73.8 7972.7 83 68.3 60.9 46.2 67.2 80 64.8 69.8 62.6 64.4 53.8 68.9 81 64.269.8 61.8 66.7 76.9 62.3 82 66.5 69.8 65 69 76.9 65.6 83 60.8 52.8 64.270.1 65.4 72.1

TABLE 4 SEQ ID NO: Discriminant coefficient Constant term 1 3.10 39.85 22.84 16.65 3 2.22 13.44 4 1.76 10.14 5 2.75 16.32 6 3.19 22.93 7 6.9364.26 8 3.85 31.55 9 2.35 17.01 10 2.72 16.12 11 3.83 24.06 12 3.6427.80 13 3.40 27.68 14 3.50 36.83 15 1.68 9.99 16 2.03 13.73 17 2.7919.34 18 2.79 17.67 19 3.46 23.85 20 2.16 12.27 21 1.69 11.03 22 2.2219.50 23 1.82 14.51 24 2.08 13.00 25 2.36 17.76 26 4.24 50.31 27 2.1915.19 28 2.97 17.23 29 2.73 15.72 30 4.77 60.37 31 2.88 16.50 32 3.3640.40 33 4.45 47.32 34 3.10 26.84 35 2.73 22.91 36 3.64 26.76 37 2.0421.42 38 3.84 30.11 39 2.80 20.07 40 3.78 31.18 41 3.93 28.97 42 3.8727.95 43 3.61 27.20 44 4.63 58.85 45 1.91 10.91 46 2.27 24.74 47 2.5715.29 48 5.47 46.73 49 1.56 10.17 50 1.61 10.45 51 1.31 7.87 52 3.0321.43 53 1.93 11.42 54 3.60 47.33 55 2.26 18.49 56 2.73 29.67 57 1.8714.47 58 2.21 18.13 59 2.26 13.31 60 5.71 76.75 61 2.63 15.46 62 1.126.78 63 1.37 8.50 64 3.59 30.25 65 2.51 15.04 66 4.85 54.20 67 2.4215.94 68 2.46 21.44 69 3.86 43.50 70 2.76 28.72 71 1.34 13.78 72 2.5715.69 73 2.33 14.12 74 2.22 13.04 75 1.22 6.90 76 1.12 6.52 77 1.35 7.6678 2.49 14.91 79 2.22 17.09 80 2.59 17.43 81 2.64 17.94 82 1.95 11.84 833.21 44.93

TABLE 5-1 Training cohort Sample Stage of name Disease progression CEA(ng/mL) CA19-9 (U/mL) IP013 IPMC 4.6 66.6 IP023 IPMC 4.7 8 IP063 IPMC 3193.4 IP147 IPMC 3.2 183.3 IP148 IPMC 11.9 1158 IP149 IPMA high grade3.6 35.6 IP151 IPMA high grade 2.3 0.1 IP153 IPMA low grade 3.5 4.4IP154 IPMA low grade 1.8 7.2 IP157 IPMA high grade 4 0.1 IP159 IPMC 6.122.8 IP160 IPMC 2.8 26.1 IP161 IPMC 2.7 16.8 IP166 IPMA low grade 1.12.9 IP167 IPMA high grade 4.5 0.6 IP168 IPMA low grade 2.4 17 IP172 IPMC6.2 60.2 IP175 IPMC 7.5 2246 IP178 IPMC 1.9 30 IP182 IPMA high gradeIP205 IPMC P_06 Early 2b 1.7 435.1 P_07 pancreatic 2b 1 149.8 P_09cancer 2b 3.5 22100 P_10 2b 0.8 62 P_11 2a 2.7 0.4 P_13 2a 4.6 66.6 P_152a 2.4 735 P_18 2a 1.9 33.6 P_19 2b 8.9 47.1 P_20 2b 1.7 30.3 P_21 2b14.8 22.3 P_25 2b 12.1 3274 P_27 2b 4.6 282.8 P_29 2a 1.5 37.8 P_30 2a1.7 20.9 P_31 2a 2.1 387.9 P_32 2a 1.1 15.4 P_33 2b 3.1 160.6 P_35 2b0.3 9.9 P_40 2b 1.4 221.5 P_42 2b 34.6 168.8 P_45 2b 9.1 569 P_46 2b 3.380.5 P_47 2b 1.8 97.5 P_48 2b 3.1 405.7 P_50 2b 0.9 8.1 P_51 2a 2.3 2118P_54 2b 1.9 250.4 P_56 2b 3.3 1870 P_59 2b 2.1 95.1 P_60 2b 3.4 79.2Sensitivity (%) 18 58

TABLE 5-2 Validation cohort Sample Stage of name Disease progression CEA(ng/mL) CA19-9 (U/mL) IP008 IPMC 1.8 19.5 IP155 IPMA low grade 1.9 18.6IP156 IPMA high grade 0.7 8.8 IP162 IPMA high grade 1.5 10.9 IP163 IPMC3 103.4 IP164 IPMA high grade 3.5 122.9 IP165 IPMC 5.6 401.7 IP169 IPMC3.1 1143 IP170 IPMA low grade 1 7.1 IP173 IPMC 2.7 51.3 IP174 IPMC 3.923.2 IP176 IPMA low grade 2.2 28.3 P_01 Early 2b 4.5 55.9 P_02pancreatic 2b 2.6 327.6 P_04 cancer 2b 4.1 950 P_14 2b 3.2 137.8 P_28 2a3.8 348.8 P_36 2b 5.2 1251 P_52 2b 2.8 41.6 P_53 2b 4 279.9 P_55 2a 6.42848 P_57 2b 5.9 454.3 P_58 2a 2.1 0.1 P_61 2b 10.3 283.5 P_62 2b 4.2268 Sensitivity (%) 20 68

TABLE 6 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 1_2 90.3 98.1 87 87.4 92.3 85.2 1_3 96.6 96.2 96.7 94.3 88.596.7 1_4 90.3 96.2 87.8 85.1 84.6 85.2 1_5 92.6 96.2 91.1 87.4 88.5 86.91_6 89.8 96.2 87 83.9 84.6 83.6 1_7 90.9 94.3 89.4 86.2 88.5 85.2 1_893.2 96.2 91.9 89.7 84.6 91.8 1_9 89.8 96.2 87 85.1 80.8 86.9 1_10 93.294.3 92.7 88.5 88.5 88.5 1_11 93.8 96.2 92.7 87.4 84.6 88.5 1_12 89.896.2 87 86.2 84.6 86.9 1_13 90.3 96.2 87.8 85.1 84.6 85.2 1_14 89.8 96.287 83.9 80.8 85.2 1_15 94.3 92.5 95.1 90.8 80.8 95.1 1_16 89.8 96.2 8785.1 84.6 85.2 1_17 92 96.2 90.2 83.9 84.6 83.6 1_18 95.5 94.3 95.9 89.784.6 91.8 1_19 92.6 94.3 91.9 88.5 88.5 88.5 1_20 95.5 94.3 95.9 93.188.5 95.1 1_21 93.7 90.4 95.1 94.3 88.5 96.7 1_22 89.2 94.3 87 81.6 76.983.6 1_23 90.3 96.2 87.8 85.1 84.6 85.2 1_24 95.5 94.3 95.9 90.8 88.591.8 1_25 90.9 96.2 88.6 83.9 84.6 83.6 1_26 90.9 94.3 89.4 83.9 80.885.2 1_27 90.3 96.2 87.8 85.1 84.6 85.2 1_28 94.3 94.3 94.3 95.4 96.295.1 1_29 89.8 96.2 87 86 80.8 88.3 1_30 90.3 96.2 87.8 85.1 84.6 85.21_31 90.9 96.2 88.6 87.4 84.6 88.5 1_32 89.2 96.2 86.2 85.1 84.6 85.21_33 90.3 96.2 87.8 85.1 84.6 85.2 1_34 89.8 96.2 87 85.1 84.6 85.2 1_3592 94.3 91.1 87.4 88.5 86.9 1_36 89.8 96.2 87 85.1 84.6 85.2 1_37 88.696.2 85.4 85.1 84.6 85.2 1_38 89.8 96.2 87 85.1 84.6 85.2 1_39 93.2 94.392.7 85.1 80.8 86.9 1_40 92.6 94.3 91.9 83.9 80.8 85.2 1_41 89.8 96.2 8783.9 88.5 82 1_42 90.3 96.2 87.8 88.5 88.5 88.5 1_43 89.8 96.2 87 85.184.6 85.2 1_44 90.3 96.2 87.8 85.1 84.6 85.2 1_45 89.2 96.2 86.2 83.984.6 83.6 1_46 91.5 96.2 89.4 85.1 84.6 85.2 1_47 90.9 94.3 89.4 82.880.8 83.6 1_48 92 94.3 91.1 82.8 80.8 83.6 1_49 90.3 96.2 87.8 85.1 84.685.2 1_50 94.3 92.5 95.1 90.8 84.6 93.4 1_51 89.2 96.2 86.2 85.1 84.685.2 1_52 92 94.3 91.1 85.1 84.6 85.2 1_53 93.2 94.3 92.7 88.5 84.6 90.21_54 91.5 96.2 89.4 85.1 84.6 85.2 1_55 89.2 96.2 86.2 85.1 84.6 85.21_56 90.3 96.2 87.8 85.1 84.6 85.2 1_57 89.8 96.2 87 82.8 84.6 82 1_5890.3 96.2 87.8 85.1 84.6 85.2 1_59 90.9 94.3 89.4 85.1 84.6 85.2 1_6090.3 96.2 87.8 85.1 84.6 85.2 1_61 93.2 94.3 92.7 89.7 84.6 91.8 1_6293.8 92.5 94.3 93.1 88.5 95.1 1_63 94.9 94.3 95.1 89.7 80.8 93.4 1_6491.5 94.3 90.2 82.8 80.8 83.6 1_65 92.6 94.3 91.9 89.7 84.6 91.8 1_6689.2 96.2 86.2 85.1 84.6 85.2 1_67 89.2 96.2 86.2 85.1 84.6 85.2 1_6889.8 96.2 87 85.1 84.6 85.2 1_69 93.2 94.3 92.7 87.4 84.6 88.5 1_70 89.894.3 87.8 85.1 84.6 85.2 1_71 89.8 96.2 87 84.9 84 85.2 1_72 93.2 94.392.7 90.8 84.6 93.4 1_73 89.8 96.2 87 83.9 84.6 83.6 1_74 92 94.3 91.187.4 88.5 86.9 1_75 92 96.2 90.2 83.9 76.9 86.9 1_76 90.3 96.2 87.8 85.184.6 85.2 1_77 91.5 96.2 89.4 83.9 84.6 83.6 1_78 90.9 96.2 88.6 83.984.6 83.6 1_79 89.8 96.2 87 83.9 84.6 83.6 1_80 91.5 96.2 89.4 85.1 84.685.2 1_81 93.2 94.3 92.7 87.4 84.6 88.5 1_82 94.3 94.3 94.3 86.2 80.888.5 1_83 91.5 96.2 89.4 85.1 84.6 85.2 1_84 95.5 100 93.5 90.8 96.288.5 1_85 97.2 100 95.9 97.7 100 96.7 1_86 96.6 96.2 96.7 93.1 84.6 96.71_87 96.6 100 95.1 95.4 100 93.4 1_88 96.6 98.1 95.9 93.1 92.3 93.4 1_8996 98.1 95.1 89.7 88.5 90.2 1_90 92.6 100 89.4 92 100 88.5 1_91 94.996.2 94.3 90.8 88.5 91.8 1_92 94.9 92.5 95.9 95.4 96.2 95.1 1_93 93.296.2 91.9 88.5 84.6 90.2 1_94 94.3 96.2 93.5 90.8 84.6 93.4 1_95 89.296.2 86.2 85.1 84.6 85.2 1_96 94.3 92.5 95.1 90.8 84.6 93.4 1_97 94.396.2 93.5 90.8 96.2 88.5 1_98 95.5 96.2 95.1 93.1 88.5 95.1 1_99 92 96.290.2 85.1 88.5 83.6 1_100 89.2 96.2 86.2 85.1 84.6 85.2 1_101 90.3 96.287.8 88.5 88.5 88.5 1_102 96 98.1 95.1 90.8 92.3 90.2 1_103 92 96.2 90.287.4 84.6 88.5 1_104 94.3 94.3 94.3 87.4 80.8 90.2 1_105 94.9 94.3 95.194.3 88.5 96.7 1_106 88.6 96.2 85.4 87.2 88 86.9 1_107 94.3 94.3 94.385.1 76.9 88.5 1_108 89.2 96.2 86.2 83.9 80.8 85.2 1_109 96 94.3 96.794.3 88.5 96.7 1_110 88.6 96.2 85.4 85.1 84.6 85.2 1_111 93.8 96.2 92.789.7 80.8 93.4 1_112 90.3 96.2 87.8 86.2 80.8 88.5 1_113 92 96.2 90.287.4 88.5 86.9 1_114 90.3 96.2 87.8 85.1 84.6 85.2 1_115 93.8 96.2 92.792 96.2 90.2 1_116 92 96.2 90.2 88.5 80.8 91.8 1_117 96.6 96.2 96.7 88.588.5 88.5 1_118 93.2 94.3 92.7 87.4 88.5 86.9 1_119 89.8 96.2 87 87.484.6 88.5 1_120 89.8 96.2 87 85.1 84.6 85.2 1_121 93.8 94.3 93.5 92 96.290.2 1_122 92 96.2 90.2 85.1 88.5 83.6 1_123 90.3 94.3 88.6 89.7 84.691.8 1_124 88.6 96.2 85.4 83.9 84.6 83.6 1_125 96 92.5 97.6 92 92.3 91.81_126 89.2 96.2 86.2 86.2 88.5 85.2 1_127 92 94.3 91.1 83.9 80.8 85.21_128 88.6 96.2 85.4 85.1 84.6 85.2 1_129 94.9 100 92.7 94.3 96.2 93.41_130 89.2 96.2 86.2 86.2 88.5 85.2 1_131 90.9 96.2 88.6 87.4 88.5 86.91_132 91.5 94.3 90.2 87.4 88.5 86.9 1_133 92 96.2 90.2 87.4 88.5 86.91_134 91.5 96.2 89.4 85.1 84.6 85.2 1_135 90.9 96.2 88.6 88.5 88.5 88.51_136 88.1 96.2 84.6 83.9 84.6 83.6 1_137 90.9 96.2 88.6 88.5 84.6 90.21_138 89.2 96.2 86.2 85.1 84.6 85.2 1_139 90.3 96.2 87.8 86.2 88.5 85.21_140 92.6 96.2 91.1 87.4 88.5 86.9 1_141 96 100 94.3 92 96.2 90.2 1_14292 96.2 90.2 85.1 84.6 85.2 1_143 93.8 94.3 93.5 92 84.6 95.1 1_144 89.894.3 87.8 85.1 84.6 85.2 1_145 92.6 94.3 91.9 86.2 84.6 86.9 1_146 90.396.2 87.8 85.1 84.6 85.2 1_147 92.6 96.2 91.1 89.7 96.2 86.9 1_148 89.896.2 87 85.1 84.6 85.2 1_149 89.2 96.2 86.2 85.1 84.6 85.2 1_150 92.694.3 91.9 86.2 88.5 85.2 1_151 90.3 96.2 87.8 85.1 84.6 85.2 1_152 93.296.2 91.9 89.7 88.5 90.2 1_153 89.8 96.2 87 87.4 84.6 88.5 1_154 89.296.2 86.2 85.1 88.5 83.6 1_155 91.4 96.2 89.3 85.1 84.6 85.2 1_156 89.296.2 86.2 85.1 84.6 85.2 1_157 91.5 96.2 89.4 83.9 84.6 83.6 1_158 90.394.3 88.6 85.1 88.5 83.6 1_159 89.8 96.2 87 85.1 84.6 85.2 1_160 92 94.391.1 85.1 80.8 86.9 1_161 96 94.3 96.7 92 88.5 93.4 1_162 89.8 96.2 8785.1 84.6 85.2 1_163 90.3 96.2 87.8 85.1 84.6 85.2 1_164 93.8 94.3 93.590.8 84.6 93.4 1_165 90.3 96.2 87.8 85.1 84.6 85.2 1_166 94.3 92.5 95.190.8 84.6 93.4 1_167 89.8 96.2 87 85.1 84.6 85.2 1_168 93.2 96.2 91.988.5 88.5 88.5 1_169 89.8 96.2 87 85.1 88.5 83.6 1_170 89.8 96.2 87 82.884.6 82 1_171 89.8 96.2 87 85.1 84.6 85.2 1_172 90.3 96.2 87.8 85.1 84.685.2 1_173 92 96.2 90.2 86.2 88.5 85.2 1_174 91.4 96.2 89.4 86.2 88.585.2 1_175 89.8 96.2 87 85.1 84.6 85.2 1_176 89.2 96.2 86.2 85.1 84.685.2 1_177 90.3 96.2 87.8 86.2 88.5 85.2 1_178 92.6 94.3 91.9 85.1 84.685.2 1_179 91.5 96.2 89.4 87.4 88.5 86.9 1_180 90.3 94.3 88.6 83.9 84.683.6 1_181 92 96.2 90.2 86.2 88.5 85.2 1_182 91.5 94.3 90.2 87.4 88.586.9 1_183 89.8 96.2 87 85.1 84.6 85.2 1_184 89.2 96.2 86.2 85.1 84.685.2 1_185 89.8 96.2 87 85.1 84.6 85.2 1_186 88.6 96.2 85.4 85.1 84.685.2 1_187 90.3 94.3 88.6 85.1 84.6 85.2 1_188 88.6 96.2 85.4 85.1 84.685.2 1_189 89.2 94.3 87 82.8 80.8 83.6 1_190 93.2 94.3 92.7 88.5 84.690.2 1_191 89.8 92.5 88.6 86.2 88.5 85.2 1_192 94.3 96.2 93.5 89.7 88.590.2 1_193 88.6 94.3 86.2 83.9 84.6 83.6 1_194 92.6 92.5 92.7 90.8 84.693.4 1_195 94.3 96.2 93.5 86.2 76.9 90.2 1_196 92 94.3 91.1 86.2 88.585.2 1_197 89.8 96.2 87 82.8 84.6 82 1_198 89.8 96.2 87 85.1 84.6 85.21_199 92.6 96.2 91.1 90.8 80.8 95.1 1_200 90.3 96.2 87.8 85.1 84.6 85.21_201 90.9 96.2 88.6 85.1 84.6 85.2 1_202 89.8 96.2 87 85.1 84.6 85.21_203 89.8 96.2 87 85.1 80.8 86.9 1_204 91.5 96.2 89.4 85.1 84.6 85.21_205 93.2 92.5 93.5 89.7 88.5 90.2 1_206 89.2 96.2 86.2 85.1 84.6 85.21_207 92 96.2 90.2 89.7 84.6 91.8 1_208 89.8 94.3 87.8 85.1 84.6 85.21_209 89.2 96.2 86.2 82.8 84.6 82 1_210 93.2 96.2 91.9 88.5 84.6 90.21_211 90.9 96.2 88.6 85.1 84.6 85.2 1_212 90.9 96.2 88.6 85.1 84.6 85.21_213 89.8 96.2 87 85.1 84.6 85.2 1_214 89.2 94.3 87 85.1 84.6 85.21_215 89.8 96.2 87 85.1 84.6 85.2 1_216 89.1 96.2 86.2 85.1 84.6 85.21_217 88.6 96.2 85.4 83.9 84.6 83.6 1_218 89.8 96.2 87 85.1 84.6 85.21_219 90.3 96.2 87.8 85.1 84.6 85.2 1_220 90.3 96.2 87.8 85.1 84.6 85.21_221 93.8 94.3 93.5 86.2 84.6 86.9 1_222 89.8 94.3 87.8 85.1 84.6 85.21_223 91.4 96.2 89.3 85.1 84.6 85.2 1_224 88.6 96.2 85.4 85.1 84.6 85.21_225 90.9 96.2 88.6 85.1 84.6 85.2 1_226 91.5 96.2 89.4 85.1 84.6 85.2

TABLE 7 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 2_18 98.9 100 98.4 97.7 100 96.7 2_53 98.9 98.1 99.2 97.7 10096.7 2_20 98.9 96.2 100 98.9 100 98.4 2_3 98.3 98.1 98.4 98.9 100 98.42_50 98.3 98.1 98.4 98.9 100 98.4 85_3 98.9 100 98.4 100 100 100 84_398.9 98.1 99.2 97.7 100 96.7 90_3 98.3 100 97.6 98.9 100 98.4 87_3 97.7100 96.7 98.9 100 98.4 3_137 97.7 94.3 99.2 100 100 100 90_18 99.4 10099.2 97.7 100 96.7 87_18 98.9 98.1 99.2 98.9 100 98.4 89_18 98.3 96.299.2 98.9 100 98.4 18_137 98.3 94.3 100 98.9 96.2 100 84_18 97.7 98.197.6 96.6 100 95.1 86_12 97.2 96.2 97.6 97.7 92.3 100 109_12 97.2 96.297.6 96.6 92.3 98.4 85_12 96.6 100 95.1 97.7 100 96.7 88_12 96.6 10095.1 94.3 92.3 95.1 105_12 96.6 98.1 95.9 97.7 92.3 100 85_20 98.3 10097.6 100 100 100 84_20 98.3 98.1 98.4 97.7 100 96.7 106_20 98.3 98.198.4 97.7 92 100 90_20 97.7 100 96.7 98.9 100 98.4 87_20 97.7 98.1 97.696.6 100 95.1 87_15 98.9 100 98.4 98.9 100 98.4 85_15 98.3 96.2 99.2 100100 100 2_15 97.7 98.1 97.6 97.7 100 96.7 88_15 97.2 94.3 98.4 100 100100 15_137 97.2 94.3 98.4 97.7 96.2 98.4 85_50 98.3 98.1 98.4 100 100100 87_50 97.7 100 96.7 97.7 100 96.7 84_50 97.7 98.1 97.6 97.7 100 96.7106_50 97.7 96.2 98.4 98.8 96 100 90_50 97.2 98.1 96.7 97.7 100 96.72_63 98.3 98.1 98.4 100 100 100 85_63 97.7 100 96.7 100 100 100 90_6397.7 100 96.7 97.7 100 96.7 84_63 97.7 98.1 97.6 94.3 92.3 95.1 87_6397.2 100 95.9 97.7 100 96.7 84_72 98.3 100 97.6 97.7 100 96.7 85_72 97.7100 96.7 100 100 100 88_72 97.7 100 96.7 97.7 96.2 98.4 87_72 97.7 98.197.6 98.9 100 98.4 93_72 97.7 98.1 97.6 94.3 92.3 95.1 94_5 98.3 96.299.2 94.3 92.3 95.1 85_5 97.7 98.1 97.6 97.7 100 96.7 87_5 97.2 100 95.994.3 100 91.8 5_107 97.2 94.3 98.4 93.1 84.6 96.7 84_5 96.6 100 95.193.1 96.2 91.8 85_24 97.2 94.3 98.4 100 100 100 87_24 96.6 94.3 97.697.7 100 96.7 89_24 96.6 94.3 97.6 96.6 92.3 98.4 90_24 96.6 92.5 98.498.9 100 98.4 102_24 96.6 92.5 98.4 97.7 100 96.7 85_10 97.7 96.2 98.4100 100 100 87_10 97.7 94.3 99.2 98.9 100 98.4 90_10 97.2 96.2 97.6 96.696.2 96.7 88_10 97.2 92.5 99.2 100 100 100 2_10 96.6 94.3 97.6 96.6 96.296.7 85_52 98.3 100 97.6 97.7 100 96.7 88_52 98.3 100 97.6 100 100 10087_52 97.7 100 96.7 94.3 100 91.8 98_52 97.7 98.1 97.6 96.6 96.2 96.784_52 97.2 98.1 96.7 94.3 96.2 93.4 87_9 98.3 100 97.6 95.4 100 93.489_9 97.7 100 96.7 93.1 92.3 93.4 85_9 97.2 100 95.9 96.6 96.2 96.7117_9 97.2 98.1 96.7 97.7 100 96.7 88_9 96.6 98.1 95.9 94.3 96.2 93.487_11 98.3 100 97.6 95.4 100 93.4 85_11 98.3 98.1 98.4 98.9 100 98.489_11 98.3 98.1 98.4 93.1 92.3 93.4 102_11 98.3 98.1 98.4 98.9 100 98.484_11 97.7 98.1 97.6 94.3 96.2 93.4 85_19 98.9 100 98.4 98.9 96.2 10087_19 98.3 100 97.6 97.7 100 96.7 88_19 98.3 100 97.6 98.9 96.2 10089_19 97.7 100 96.7 97.7 96.2 98.4 106_19 97.2 98.1 96.7 95.3 92 96.787_39 98.9 100 98.4 98.9 100 98.4 85_39 97.7 98.1 97.6 98.9 96.2 10088_39 97.2 96.2 97.6 96.6 92.3 98.4 84_39 96.6 98.1 95.9 94.3 92.3 95.12_39 96.6 98.1 95.9 97.7 100 96.7 87_61 97.2 100 95.9 98.9 100 98.485_61 96.6 98.1 95.9 100 100 100 88_61 96.6 98.1 95.9 100 100 100 108_6196 94.3 96.7 86.2 73.1 91.8 93_61 96 92.5 97.6 94.3 84.6 98.4 88_7 97.7100 96.7 100 100 100 85_7 97.2 100 95.9 100 100 100 87_7 97.2 100 95.997.7 100 96.7 86_7 97.2 96.2 97.6 97.7 92.3 100 91_7 96.6 96.2 96.7 98.9100 98.4 85_17 98.3 100 97.6 97.7 100 96.7 87_17 97.7 100 96.7 95.4 10093.4 89_17 96.6 94.3 97.6 94.3 88.5 96.7 102_17 96.6 94.3 97.6 97.7 96.298.4 84_17 96 100 94.3 93.1 92.3 93.4 85_22 98.9 100 98.4 97.7 96.2 98.487_22 98.9 100 98.4 98.9 100 98.4 102_22 97.7 96.2 98.4 94.3 84.6 98.489_22 97.2 98.1 96.7 93.1 88.5 95.1 117_22 97.2 96.2 97.6 95.4 96.2 95.185_26 98.9 100 98.4 96.6 96.2 96.7 87_26 98.3 100 97.6 96.6 100 95.188_26 97.2 100 95.9 95.4 92.3 96.7 84_26 96 100 94.3 95.4 100 93.4 94_2696 98.1 95.1 90.8 88.5 91.8 85_74 98.9 100 98.4 100 100 100 2_74 97.7100 96.7 97.7 100 96.7 87_74 97.2 100 95.9 97.7 100 96.7 84_74 96.6 96.296.7 95.4 100 93.4 88_74 96.6 96.2 96.7 97.7 100 96.7 90_21 97.1 94.298.4 98.9 100 98.4 2_21 97.1 94.2 98.4 97.7 96.2 98.4 106_21 97.1 92.399.2 97.7 92 100 84_21 96.6 94.2 97.6 96.6 100 95.1 85_21 96.6 92.3 98.4100 100 100 85_28 97.7 98.1 97.6 100 100 100 84_28 97.2 96.2 97.6 96.6100 95.1 86_28 96.6 94.3 97.6 96.6 92.3 98.4 87_28 96.6 94.3 97.6 98.9100 98.4 93_28 96.6 92.5 98.4 100 100 100

Example 3

<Selection of Gene Markers Using all Samples and Method for EvaluatingEarly Pancreatic Cancer or Pancreatic Cancer Precursor LesionDiscriminant Performance of Acquired Gene Markers>

In this Example, the samples of the training cohort and the validationcohort used in Examples 1 and 2 were integrated, and selection of a genemarker and evaluation of its early pancreatic cancer or pancreaticcancer precursor lesion discriminant performance were conducted usingall of the samples.

Specifically, the miRNA expression levels in the sera of the pancreaticcancer precursor lesion patients (33 persons), early pancreatic cancerpatients (44 persons) and the healthy subjects (184 persons) obtained inthe preceding Reference Examples were normalized by globalnormalization. In order to acquire diagnosis markers with higherreliability, only genes having a gene expression level of 2⁶ or higherin 50% or more of the samples in either of the early pancreatic canceror pancreatic cancer precursor lesion patient group or the healthysubject group were selected in the gene marker selection. In order tofurther acquire statistical significance for discriminating an earlypancreatic cancer or pancreatic cancer precursor lesion patient groupfrom a healthy subject group, the P value obtained by two-tailed t-testassuming equal variance as to each gene expression level was correctedby the Bonferroni method, and genes that satisfied p<0.01 were selectedas gene markers for use in explanatory variables of a discriminant anddescribed in Table 8. In this way, hsa-miR-6794-5p, hsa-miR-6511a-5p,hsa-miR-6824-5p, hsa-miR-762, hsa-miR-6836-3p, hsa-miR-6727-5p,hsa-miR-4739, hsa-miR-7977, hsa-miR-4484, hsa-miR-6515-3p,hsa-miR-373-5p, hsa-miR-4258, hsa-miR-4674, hsa-miR-3180, hsa-miR-6076,hsa-miR-1238-5p, hsa-miR-4463, hsa-miR-4486, and hsa-miR-4730 genes, andthe nucleotide sequences of SEQ ID NOs: 227 to 245 related thereto werefound in addition to the genes described in Table 2. As with thenucleotide sequences of SEQ ID NOs: 1 to 226, the results obtained aboutthe polynucleotides shown in SEQ ID NOs: 227 to 245 also showed that themeasurement values were significantly lower (decrease) or higher(increase) in the early pancreatic cancer or pancreatic cancer precursorlesion patient group than in the healthy subject group (Table 8). Theseresults were able to be validated in the validation cohort. Thus, thepresence or absence of early pancreatic cancer or pancreatic cancerprecursor lesion in the newly obtained samples can be determined by themethods described in Examples 1 and 2 by using, alone or in combination,the gene expression level measurement values described in Table 8.

TABLE 8 Change in expression level in early pancreatic cancer P valueafter and pancreatic cancer SEQ ID Bonferroni precursor lesion patientNO: Gene name correction relative to healthy subject 227 hsa-miR-6794-5p1.19E−03 Decrease 228 hsa-miR-6511a-5p 1.44E−03 Decrease 229hsa-miR-6824-5p 2.18E−03 Decrease 230 hsa-miR-762 2.05E−07 Increase 231hsa-miR-6836-3p 9.60E−07 Increase 232 hsa-miR-6727-5p 1.30E−06 Increase233 hsa-miR-4739 5.12E−06 Increase 234 hsa-miR-7977 1.01E−05 Decrease235 hsa-miR-4484 1.38E−05 Increase 236 hsa-miR-6515-3p 4.31E−04 Decrease237 hsa-miR-373-5p 6.79E−04 Increase 238 hsa-miR-4258 9.00E−04 Increase239 hsa-miR-4674 9.95E−04 Increase 240 hsa-miR-3180 1.43E−03 Increase241 hsa-miR-6076 2.65E−03 Decrease 242 hsa-miR-1238-5p 2.77E−03 Decrease243 hsa-miR-4463 3.16E−03 Increase 244 hsa-miR-4486 6.37E−03 Increase245 hsa-miR-4730 9.34E−03 Increase

Example 4

<Method for Evaluating Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion-Specific Discriminant Performance by Combination ofPlurality of Gene Markers Using Samples of Validation Cohort>

In this Example, gene expression levels of miRNAs in sera were comparedbetween a pancreatic cancer precursor lesion patient group and an earlypancreatic cancer patient group as positive control groups and a healthysubject group, an advanced pancreatic cancer patient group, a bile ductcancer patient group, a breast cancer patient group, a prostate cancerpatient group, a colorectal cancer patient group, a stomach cancerpatient group, an esophageal cancer patient group, a liver cancerpatient group, a benign pancreatic disease patient group, and a benignprostatic disease patient group as negative control groups in the sameway as the method described in Example 1 with respect to the trainingcohort as the sample group described in Reference Example 2 to select anadditional gene marker for diagnosis. The additional gene marker fordiagnosis (SEQ ID NOs: 246 to 247) thus selected was combined with thegene markers selected in Example 1 to study a method for evaluatingearly pancreatic cancer or pancreatic cancer precursor lesion-specificdiscriminant performance.

Specifically, first, the miRNA expression levels of the training cohortand the validation cohort obtained in Reference Example 2 mentionedabove were combined and normalized by global normalization. Next,Fisher's discriminant analysis was conducted as to combinations of 1 to5 expression level measurement values comprising at least one of theexpression level measurement values of the newly found polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 1 to83, 227 to 229, 246, 248, and 250 among the polynucleotides consistingof the nucleotide sequences represented by SEQ ID NOs: 1 to 250, toconstruct a discriminant for determining the presence or absence ofearly pancreatic cancer or a pancreatic cancer precursor lesion. Next,accuracy, sensitivity, and specificity in the validation cohort werecalculated using the discriminant thus prepared, with the pancreaticcancer precursor lesion patient group and the early pancreatic cancerpatient group as positive control groups and the healthy subject group,the advanced pancreatic cancer patient group, the bile duct cancerpatient group, the breast cancer patient group, the prostate cancerpatient group, the colorectal cancer patient group, the stomach cancerpatient group, the esophageal cancer patient group, the liver cancerpatient group, the benign pancreatic disease patient group, and thebenign prostatic disease patient group as negative sample groups. Thediscriminant performance of the selected polynucleotides was validatedusing independent samples.

Most of polynucleotides consisting of the nucleotide sequencesrepresented by these SEQ ID NOs (SEQ ID NOs: 1 to 250 corresponding tothe miRNA markers of Table 1) or complementary sequences thereofmentioned above were able to provide relatively high accuracy,sensitivity, and specificity in the determination of the presence orabsence of early pancreatic cancer or a pancreatic cancer precursorlesion, and furthermore, were able to specifically discriminate earlypancreatic cancer or a pancreatic cancer precursor lesion from the othercancers and benign diseases. For example, among the combinations ofmultiple polynucleotides selected from the group consisting ofpolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 119, 12, 28, 105, 137, 121, 109, 87, 5, 140, 106, 2, 175,90, 237, 247, 103, 97, 124, 92, 100, 32, 1, 246, 84, 13, 85, 153, 111,86, 141, 54, and 24 or complementary sequences thereof (the cancertype-specific polynucleotide group 1) as polynucleotides capable ofspecifically binding to target markers, combinations comprising at leastone polynucleotides preferably selected from the group consisting ofpolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 119, 12, 28, 105, 137, 121, 109, 87, 5, 140, 106, 2, 175,90, 237, and 247 or complementary sequences thereof (the cancertype-specific polynucleotide group 2) included in the cancertype-specific polynucleotide group 1 were able to specificallydiscriminate early pancreatic cancer or a pancreatic cancer precursorlesion from the other cancers and benign diseases with high accuracy.

The number of the polynucleotides with cancer type specificity in thecombination mentioned above can be 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or morefor the combination. The combinations of 4 or more of thesepolynucleotides were able to exhibit discrimination accuracy of 92% orhigher or 95% or higher.

The probes used in the measurement were the above-defined nucleic acidscapable of specifically binding to each polynucleotide as a targetmarker.

Specifically, the discrimination results of the measurement using thepolynucleotide consisting of the nucleotide sequence represented by SEQID NO: 12 or a complementary sequence thereof as a target marker areshown in Table 9-1. The measurement using one polynucleotide consistingof the nucleotide sequence represented by SEQ ID NO: 12 or acomplementary sequence thereof exhibited accuracy of 82.6% in thetraining cohort and accuracy of 82% in the validation cohort. Also, forexample, the measurement using the combination of two polynucleotidescomprising one polynucleotide consisting of the nucleotide sequencerepresented by SEQ ID NO: 12 or a complementary sequence thereofexhibited accuracy of 87% in the training cohort and accuracy of 88% inthe validation cohort. Furthermore, for example, the measurement usingthe combination of three polynucleotides comprising one polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 12 or acomplementary sequence thereof exhibited accuracy of 91.4% in thetraining cohort and accuracy of 86.6% in the validation cohort.Furthermore, for example, the measurement using the combination of fourpolynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 12 or a complementarysequence thereof exhibited accuracy of 95.6% in the training cohort andaccuracy of 95.1% in the validation cohort. Furthermore, for example,the measurement using the combination of five polynucleotides comprisingone polynucleotide consisting of the nucleotide sequence represented bySEQ ID NO: 12 or a complementary sequence thereof exhibited the highestaccuracy of 98.8% in the training cohort and the highest accuracy of98.9% in the validation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotide consisting of the nucleotide sequence represented by SEQID NO: 28 or a complementary sequence thereof as a target marker areshown in Table 9-2. The measurement using one polynucleotide consistingof the nucleotide sequence represented by SEQ ID NO: 28 or acomplementary sequence thereof exhibited accuracy of 81.6% in thetraining cohort and accuracy of 81.7% in the validation cohort. Also,for example, the measurement using the combination of twopolynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 28 or a complementarysequence thereof exhibited accuracy of 84.9% in the training cohort andaccuracy of 85.6% in the validation cohort. Furthermore, for example,the measurement using the combination of three polynucleotidescomprising one polynucleotide consisting of the nucleotide sequencerepresented by SEQ ID NO: 28 or a complementary sequence thereofexhibited accuracy of 88.8% in the training cohort and accuracy of 86.3%in the validation cohort. Furthermore, for example, the measurementusing the combination of four polynucleotides comprising onepolynucleotide consisting of the nucleotide sequence represented by SEQID NO: 28 or a complementary sequence thereof exhibited accuracy of92.4% in the training cohort and accuracy of 93.6% in the validationcohort. Furthermore, for example, the measurement using the combinationof five polynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 28 or a complementarysequence thereof exhibited the highest accuracy of 97.7% in the trainingcohort and the highest accuracy of 98.6% in the validation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotide consisting of the nucleotide sequence represented by SEQID NO: 5 or a complementary sequence thereof as a target marker areshown in Table 9-3. The measurement using one polynucleotide consistingof the nucleotide sequence represented by SEQ ID NO: 5 or acomplementary sequence thereof exhibited accuracy of 84% in the trainingcohort and accuracy of 87% in the validation cohort. Also, for example,the measurement using the combination of two polynucleotides comprisingone polynucleotide consisting of the nucleotide sequence represented bySEQ ID NO: 5 or a complementary sequence thereof exhibited accuracy of87.9% in the training cohort and accuracy of 88.4% in the validationcohort. Furthermore, for example, the measurement using the combinationof three polynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 5 or a complementarysequence thereof exhibited accuracy of 90.4% in the training cohort andaccuracy of 90.5% in the validation cohort. Furthermore, for example,the measurement using the combination of four polynucleotides comprisingone polynucleotide consisting of the nucleotide sequence represented bySEQ ID NO: 5 or a complementary sequence thereof exhibited accuracy of93.2% in the training cohort and accuracy of 93.7% in the validationcohort. Furthermore, for example, the measurement using the combinationof five polynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 5 or a complementarysequence thereof exhibited the highest accuracy of 97.7% in the trainingcohort and the highest accuracy of 98.2% in the validation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotide consisting of the nucleotide sequence represented by SEQID NO: 2 or a complementary sequence thereof as a target marker areshown in Table 9-4. The measurement using one polynucleotide consistingof the nucleotide sequence represented by SEQ ID NO: 2 or acomplementary sequence thereof exhibited accuracy of 86.8% in thetraining cohort and accuracy of 90.5% in the validation cohort. Also,for example, the measurement using the combination of twopolynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 2 or a complementarysequence thereof exhibited accuracy of 88.4% in the training cohort andaccuracy of 90.1% in the validation cohort. Furthermore, for example,the measurement using the combination of three polynucleotidescomprising one polynucleotide consisting of the nucleotide sequencerepresented by SEQ ID NO: 2 or a complementary sequence thereofexhibited accuracy of 90.9% in the training cohort and accuracy of 92.6%in the validation cohort. Furthermore, for example, the measurementusing the combination of four polynucleotides comprising onepolynucleotide consisting of the nucleotide sequence represented by SEQID NO: 2 or a complementary sequence thereof exhibited accuracy of 93%in the training cohort and accuracy of 92.6% in the validation cohort.Furthermore, for example, the measurement using the combination of fivepolynucleotides comprising one polynucleotide consisting of thenucleotide sequence represented by SEQ ID NO: 2 or a complementarysequence thereof exhibited the highest accuracy of 97.7% in the trainingcohort and the highest accuracy of 98.2% in the validation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 12 and 28 or complementary sequences thereof as targetmarkers are shown in Table 9-5. The measurement using the combination oftwo polynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 28 orcomplementary sequences thereof exhibited accuracy of 90% in thetraining cohort and accuracy of 92.6% in the validation cohort. Also,for example, the measurement using the combination of threepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 28 orcomplementary sequences thereof exhibited accuracy of 92.3% in thetraining cohort and accuracy of 93.3% in the validation cohort.Furthermore, for example, the measurement using the combination of fourpolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 28 orcomplementary sequences thereof exhibited accuracy of 93.9% in thetraining cohort and accuracy of 93.7% in the validation cohort.Furthermore, for example, the measurement using the combination of fivepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 28 orcomplementary sequences thereof exhibited the highest accuracy of 97.9%in the training cohort and the highest accuracy of 97.9% in thevalidation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 12 and 5 or complementary sequences thereof as targetmarkers are shown in Table 9-6. The measurement using the combination oftwo polynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 5 orcomplementary sequences thereof exhibited accuracy of 91.2% in thetraining cohort and accuracy of 89.4% in the validation cohort. Also,for example, the measurement using the combination of threepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 5 orcomplementary sequences thereof exhibited accuracy of 93% in thetraining cohort and accuracy of 92.6% in the validation cohort.Furthermore, for example, the measurement using the combination of fourpolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 5 orcomplementary sequences thereof exhibited accuracy of 95.1% in thetraining cohort and accuracy of 93% in the validation cohort.Furthermore, for example, the measurement using the combination of fivepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 5 orcomplementary sequences thereof exhibited the highest accuracy of 98.1%in the training cohort and the highest accuracy of 97.9% in thevalidation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 12 and 2 or complementary sequences thereof as targetmarkers are shown in Table 9-7. The measurement using the combination oftwo polynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 2 orcomplementary sequences thereof exhibited accuracy of 91.2% in thetraining cohort and accuracy of 90.1% in the validation cohort. Also,for example, the measurement using the combination of threepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 2 orcomplementary sequences thereof exhibited accuracy of 93.9% in thetraining cohort and accuracy of 92.6% in the validation cohort.Furthermore, for example, the measurement using the combination of fourpolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 2 orcomplementary sequences thereof exhibited accuracy of 94.6% in thetraining cohort and accuracy of 93.3% in the validation cohort.Furthermore, for example, the measurement using the combination of fivepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12 and 2 orcomplementary sequences thereof exhibited the highest accuracy of 98.1%in the training cohort and the highest accuracy of 97.9% in thevalidation cohort.

Specifically, the discrimination results of the measurement using thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 5 and 2 or complementary sequences thereof as target markersare shown in Table 9-8. The measurement using the combination of twopolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 5 and 2 or complementarysequences thereof exhibited accuracy of 89.8% in the training cohort andaccuracy of 92.3% in the validation cohort. Also, for example, themeasurement using the combination of three polynucleotides comprisingthe polynucleotides consisting of the nucleotide sequences representedby SEQ ID NOs: 5 and 2 or complementary sequences thereof exhibitedaccuracy of 92.1% in the training cohort and accuracy of 94% in thevalidation cohort. Furthermore, for example, the measurement using thecombination of four polynucleotides comprising the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 5 and2 or complementary sequences thereof exhibited accuracy of 93.9% in thetraining cohort and accuracy of 95.1% in the validation cohort.Furthermore, for example, the measurement using the combination of fivepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 5 and 2 or complementarysequences thereof exhibited the highest accuracy of 97.2% in thetraining cohort and the highest accuracy of 97.9% in the validationcohort.

Specifically, the discrimination results of the measurement using thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 12, 28, and 5 or complementary sequences thereof as targetmarkers are shown in Table 9-9. The measurement using the combination ofthree polynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12, 28, and 5 orcomplementary sequences thereof exhibited accuracy of 93.3% in thetraining cohort and accuracy of 94.4% in the validation cohort. Also,for example, the measurement using the combination of fourpolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12, 28, and 5 orcomplementary sequences thereof exhibited accuracy of 94.6% in thetraining cohort and accuracy of 96.5% in the validation cohort.Furthermore, for example, the measurement using the combination of fivepolynucleotides comprising the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 12, 28, and 5 orcomplementary sequences thereof exhibited accuracy of 97.5% in thetraining cohort and accuracy of 96.8% in the validation cohort.

The expression level measurement values of the nucleotide sequencesrepresented by SEQ ID NOs: 106, 12, 137, 119, and 105 were comparedamong 21 pancreatic cancer precursor lesion patients, 31 earlypancreatic cancer patients, 128 healthy subjects, 61 advanced pancreaticcancer patients, 66 bile duct cancer patients, 51 breast cancerpatients, 35 prostate cancer patients, 31 colorectal cancer patients, 32stomach cancer patients, 34 esophageal cancer patients, 38 liver cancerpatients, 15 benign pancreatic disease patients, and 26 benign prostaticdisease patients in the training cohort. As a result, a scatter diagramthat significantly separated the discriminant score of the earlypancreatic cancer or pancreatic cancer precursor lesion patient groupfrom the discriminant scores of the other groups was obtained in thetraining cohort (see the upper diagram of FIG. 4). These results werealso reproducible in the validation cohort (see the lower diagram ofFIG. 4).

TABLE 9-1 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 12 82.6 90.6 81.8 82 76.9 82.6 12_237 87 96.2 86.1 88 92.3 87.612_85_13 91.4 100 90.5 86.6 84.6 86.8 90_12_97_140 95.6 100 95.2 95.196.2 95 12_137_119_105_237 98.4 100 98.3 97.9 100 97.7 87_12_137_119_10598.2 100 98.1 97.5 100 97.3 12_103_137_105_247 98.2 100 98.1 98.6 10098.4 12_137_119_92_105 98.2 100 98.1 97.9 100 97.7 12_137_119_105_12198.2 100 98.1 98.2 100 98.1 12_137_1_119_105 98.1 100 97.9 97.9 100 97.712_137_119_124_105 98.1 100 97.9 97.9 100 97.7 12_137_119_105_32 98.1100 97.9 98.2 100 98.1 12_137_119_105_100 98.1 100 97.9 97.9 100 97.712_137_119_105_86 98.1 100 97.9 97.9 100 97.7 12_137_119_105_153 98.1100 97.9 98.6 100 98.4 12_137_119_105_141 98.1 100 97.9 97.5 100 97.312_137_105_246_153 98.1 100 97.9 97.2 100 96.9 12_97_137_105_153 97.9100 97.7 96.8 100 96.5 12_103_137_119_105 97.9 100 97.7 97.9 100 97.712_137_119_105_246 97.9 100 97.7 98.2 100 98.1 12_137_92_105_247 97.9100 97.7 98.2 100 98.1 12_137_124_105_153 97.9 100 97.7 97.5 100 97.312_137_105_32_153 97.9 100 97.7 97.5 100 97.3 12_137_105_13_121 97.9 10097.7 97.5 100 97.3 106_12_137_119_105 98.8 100 98.6 97.5 100 97.312_137_119_105_13 98.6 100 98.4 97.9 100 97.7 12_137_119_105_140 98.6100 98.4 97.9 100 97.7 12_137_119_105_247 98.6 100 98.4 98.9 100 98.812_137_119_105_109 98.4 100 98.3 97.5 100 97.3 12_137_105_109_121 98.1100 97.9 97.5 100 97.3 12_103_137_105_121 97.9 100 97.7 97.9 100 97.712_137_105_32_121 97.9 100 97.7 97.9 100 97.7 12_137_124_105_247 98.1100 97.9 97.5 100 97.3 12_137_105_246_247 98.1 100 97.9 97.2 100 96.912_137_105_153_247 98.1 100 97.9 97.5 100 97.3 12_137_105_247_141 98.1100 97.9 97.2 100 96.9 12_137_105_247 97.9 100 97.7 97.2 100 96.912_137_105_140_247 98.1 100 97.9 97.9 100 97.7 12_119_124_105_140 98.1100 97.9 97.5 100 97.3 12_119_105_100_140 98.1 100 97.9 96.8 96.2 96.990_12_119_105_140 97.7 100 97.5 97.9 100 97.7 90_12_137_119_105 97.9 10097.7 98.2 100 98.1 90_12_137_105_32 97.9 100 97.7 97.2 100 96.990_12_137_105_153 97.9 100 97.7 96.8 100 96.5 90_12_119_105_100 97.7 10097.5 97.2 96.2 97.3 90_12_119_109_140 97.7 100 97.5 97.2 100 96.987_12_137_105_247 97.7 100 97.5 97.2 100 96.9 90_12_109_140_237 97.9 10097.7 96.1 96.2 96.1 12_137_105_109_153 97.9 100 97.7 97.2 100 96.912_137_105_109_247 97.9 100 97.7 97.9 100 97.7 12_137_109_140_247 97.998.1 97.9 96.1 96.2 96.1 12_137_109_121_237 97.9 98.1 97.9 96.8 100 96.512_137_119_105_175 98.1 100 97.9 97.9 100 97.7 12_137_109_175_121 97.5100 97.3 97.5 100 97.3 87_12_119_105_175 97.4 100 97.1 97.5 100 97.312_137_119_105_111 98.2 100 98.1 97.9 100 97.7 12_137_119_105_24 98.2100 98.1 97.9 100 97.7 12_137_105_32_247 98.2 100 98.1 98.2 100 98.190_12_137_105_237 98.1 100 97.9 96.5 100 96.1 12_84_137_119_105 98.1 10097.9 97.9 100 97.7 12_97_137_105_247 98.1 100 97.9 97.9 100 97.787_12_137_105_237 97.2 100 96.9 96.5 100 96.1 87_12_100_109_237 97.2 10096.9 95.8 100 95.3 87_12_100_109_237 97.2 100 96.9 95.8 100 95.3106_12_137_105_86 97.9 100 97.7 97.2 100 96.9 106_12_137_105_247 97.9100 97.7 97.5 100 97.3 106_12_119_105_100 97.9 100 97.7 95.7 96 95.7106_12_137_105_121 97.7 100 97.5 97.5 100 97.3

TABLE 9-2 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 28 81.6 83 81.4 81.7 96.2 80.2 103_28 84.9 84.9 84.9 85.6 96.284.5 105_28_109 88.8 88.7 88.8 86.3 96.2 85.3 84_105_28_100 92.4 94.392.2 93.6 100 93 137_119_105_28_237 97.7 98.1 97.7 98.6 100 10087_106_119_28_121 97.4 100 97.1 97.5 100 100 106_137_119_28_121 97.4 10097.1 97.5 100 100 90_119_105_28_237 97.4 98.1 97.3 97.9 100 100

TABLE 9-3 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 5 84 88.7 83.6 87 88.5 86.8 5_84 87.9 92.5 87.4 88.4 92.3 885_137_85 90.4 98.1 89.6 90.5 96.2 89.9 5_97_237_247 93.2 94.3 93 93.7100 93 90_5_137_119_105 97.7 100 97.5 98.2 100 100 5_137_119_105_23797.7 98.1 97.7 98.2 100 100 5_137_119_105_32 97.5 98.1 97.5 97.9 100 100

TABLE 9-4 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 2 86.8 96.2 85.9 90.5 96.2 89.9 2_1 88.4 98.1 87.4 90.1 96.289.5 2_87_111 90.9 100 89.9 92.6 100 91.9 2_87_90_103 93 98.1 92.5 92.6100 91.9 2_137_119_105_237 97.7 98.1 97.7 98.2 100 100 2_87_137_119_10597.4 100 97.1 97.9 100 100 2_137_119_105_13 97.4 100 97.1 98.2 100 1002_137_119_105_121 97.4 100 97.1 98.2 100 100 2_137_119_105_247 97.4 98.197.3 97.9 100 100 2_87_119_109_247 97.2 100 96.9 97.5 100 1002_90_137_119_105 97.2 100 96.9 97.5 100 100 2_137_119_105_140 97.2 10096.9 98.2 100 100 2_87_119_105_237 97.2 100 96.9 96.8 100 100

TABLE 9-5 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 12_28 90 92.5 89.7 92.6 88.5 93 12_28_32 92.3 96.2 91.9 93.392.3 93.4 12_137_28_32 93.9 100 93.2 93.7 100 93 12_137_105_28_247 97.998.1 97.9 97.5 100 100 12_137_119_105_28 97.7 100 97.5 97.9 100 10012_103_137_105_28 97.5 100 97.3 96.8 100 100 12_84_28_140_121 97.5 98.197.5 96.5 92.3 92.3 12_137_28_109_121 97.5 98.1 97.5 97.5 100 10012_1_28_121_247 97.5 98.1 97.5 96.1 96.2 96.2 12_119_28_100_121 97.598.1 97.5 97.2 100 100 12_92_28_100_247 97.5 98.1 97.5 97.2 100 10012_28_100_140_247 97.5 98.1 97.5 97.5 96.2 96.2 12_137_28_109_247 97.594.3 97.9 95.8 92.3 92.3 12_84_28_109_121 97.4 98.1 97.3 95.8 96.2 96.212_103_1_28_121 97.4 98.1 97.3 95.4 100 100 12_1_28_32_121 97.4 98.197.3 95.8 100 100 12_1_28_100_121 97.4 98.1 97.3 95.1 96.2 96.212_1_28_175_121 97.4 98.1 97.3 95.8 100 100

TABLE 9-6 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 5_12 91.2 98.1 90.5 89.4 84.6 89.9 5_12_92 93 98.1 92.5 92.696.2 92.2 5_12_105_13 95.1 98.1 94.8 93 92.3 93 5_12_137_119_105 97.9100 97.7 97.9 100 100 90_5_12_119_105 97.7 100 97.5 96.8 100 1005_12_137_105_121 97.7 100 97.5 97.5 100 100 5_12_119_92_121 97.7 10097.5 96.1 100 100 90_5_12_109_247 97.7 98.1 97.7 95.8 96.2 96.25_12_137_109_121 97.7 98.1 97.7 97.5 100 100 5_12_137_109_247 97.7 96.297.9 97.9 100 100 90_5_106_12_109 97.5 100 97.3 95.4 96 9690_5_12_137_105 97.5 100 97.3 96.8 100 100 90_5_12_119_109 97.5 100 97.396.1 100 100 90_5_12_105_109 97.5 100 97.3 96.1 100 100 5_12_137_105_15397.5 100 97.3 97.5 100 100 5_12_119_105_54 97.5 100 97.3 97.5 96.2 96.287_5_106_12_109 97.4 100 97.1 96.1 96 96 87_5_12_137_105 97.4 100 97.196.1 100 100 90_5_12_1_105 97.4 100 97.1 95.4 96.2 96.2 90_5_12_109_8697.4 100 97.1 95.4 96.2 96.2 5_12_137_105_247 98.1 100 97.9 97.5 100 10090_5_12_109_175 97.5 100 97.3 95.1 100 100 5_12_100_109_121 97.9 10097.7 96.1 96.2 96.2

TABLE 9-7 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 2_12 91.2 100 90.3 90.1 92.3 89.9 2_12_121 93.9 100 93.2 92.692.3 92.6 2_12_1_121 94.6 100 94 93.3 96.2 93 2_12_137_119_105 97.9 10097.7 97.2 100 100 2_12_137_105_153 97.9 100 97.7 96.5 100 1002_12_137_105_121 97.5 100 97.3 96.5 100 100 2_12_109_121_247 97.4 10097.1 95.4 96.2 96.2 2_90_12_119_105 97.2 100 96.9 96.8 100 1002_90_12_109_140 97.2 100 96.9 96.1 96.2 96.2 2_12_100_109_121 97.2 10096.9 95.8 96.2 96.2 2_12_109_175_121 97.2 100 96.9 95.8 96.2 96.22_12_97_105_247 97.2 98.1 97.1 95.1 96.2 96.2 2_12_137_105_247 98.1 10097.9 96.8 100 100 2_12_137_109_121 97.9 100 97.7 97.9 100 100

TABLE 9-8 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 2_5 89.8 100 88.8 92.3 100 91.5 2_5_247 92.1 98.1 91.5 94 10093.4 2_5_97_153 93.9 98.1 93.4 95.1 100 94.6 2_90_5_119_105 97.2 10096.9 97.9 100 100 2_5_119_109_121 97.2 100 96.9 97.9 100 1002_5_119_86_121 97.2 100 96.9 96.5 100 100

TABLE 9-9 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 5_12_28 93.3 96.2 93 94.4 96.2 94.2 5_12_119_28 94.6 98.1 94.296.5 100 96.1 5_12_1_28_121 97.5 98.1 97.5 96.8 100 100

Example 5

<Method for Evaluating Early Pancreatic Cancer or Pancreatic CancerPrecursor Lesion Discriminant Performance by Combination of MultipleGene Markers Using Samples in the Validation Cohort>

Example 2 showed that discriminant performance was improved by using acombination of the multiple gene markers selected in Example 1, ascompared with using one of the gene marker. Thus, in this Example, eventhe gene markers that were not selected in Example 1 were studied as towhether high early pancreatic cancer or pancreatic cancer precursorlesion discriminant performance is obtained by combinations with thegene markers selected in Example 1.

Specifically, among the genes having a gene expression level of 2⁶ orhigher in 50% or more of the samples in either of the early pancreaticcancer or pancreatic cancer precursor lesion patient group in thetraining cohort or the healthy subject group in the training cohort,genes that showed statistical significance for discriminating an earlypancreatic cancer or pancreatic cancer precursor lesion patient groupfrom a healthy subject group with the P value smaller than 0.05calculated by two-tailed t-test assuming equal variance as to each geneexpression level and corrected by the Bonferroni method, were examined.As a result, 248 genes containing the 226 genes selected in Example 1were found. Fisher's discriminant analysis was conducted as to 30,876combinations using one or two of these 248 genes, to construct adiscriminant for determining the presence or absence of early pancreaticcancer or a pancreatic cancer precursor lesion. The discriminantperformance of the selected combinations of 1 or 2 of the genes wasvalidated in the same way as the method of Example 2.

As a result, some combinations of these genes exhibited accuracy of 85%or higher in both of the training cohort and the validation cohort andare shown in Table 10. For example, the newly found polynucleotideconsisting of the nucleotide sequence represented by SEQ ID NO: 248 to250 discriminated the early pancreatic cancer or pancreatic cancerprecursor lesion patients from the healthy subjects with highdiscriminant performance when used in combination of at least twopolynucleotides comprising any of the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 1 to 226. Morespecifically, the polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NO: 248 to 250 was able to exhibit discriminationaccuracy of 85% or higher between the early pancreatic cancer orpancreatic cancer precursor lesion patients and the healthy subjects inboth of the training cohort and the validation cohort when used incombination of at least two polynucleotides comprising any of thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 2, 3, 18, 12, 20, 1, 15, 50, 63, 72, 5, 24, 10, 52, 9, 11,19, 39, 61, 7, 17, 22, 26, 74, 21, and 28. Examples of such combinationsof two genes include combinations of SEQ ID NOs: 2 and 248, SEQ ID NOs:3 and 249, SEQ ID NOs: 2 and 250, SEQ ID NOs: 1 and 249, SEQ ID NOs: 5and 250, SEQ ID NOs: 3 and 248, SEQ ID NOs: 3 and 250, SEQ ID NOs: 1 and250, SEQ ID NOs: 2 and 249, SEQ ID NOs: 21 and 248, SEQ ID NOs: 10 and248, SEQ ID NOs: 5 and 248, SEQ ID NOs: 11 and 249, SEQ ID NOs: 9 and250, SEQ ID NOs: 17 and 250, SEQ ID NOs: 21 and 249, SEQ ID NOs: 7 and250, SEQ ID NOs: 15 and 248, SEQ ID NOs: 5 and 249, SEQ ID NOs: 12 and248, SEQ ID NOs: 10 and 249, SEQ ID NOs: 28 and 250, SEQ ID NOs: 7 and249, SEQ ID NOs: 18 and 249, SEQ ID NOs: 15 and 249, SEQ ID NOs: 20 and249, SEQ ID NOs: 24 and 249, SEQ ID NOs: 11 and 250, and SEQ ID NOs: 18and 248.

As one example, an attempt was made to discriminate the early pancreaticcancer or pancreatic cancer precursor lesion patients from the healthysubjects using the expression level measurement values of the nucleotidesequences represented by SEQ ID NO: 2 and SEQ ID NO: 248. As a result,discriminant performance as high as 93.2% accuracy, 96.2% sensitivity,and 91.9% specificity in the training cohort and 95.4% accuracy, 100%sensitivity, and 93.4% specificity in the validation cohort wasobtained.

From these results, it can be concluded that all of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 248 to250 are also excellent diagnostic markers.

Table 10 mentioned above is as follows.

TABLE 10 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 2_248 93.2 96.2 91.9 95.4 100 93.4 3_249 91.5 86.8 93.5 96.6 10095.1 2_250 90.9 98.1 87.8 88.5 100 83.6 1_249 90.3 94.3 88.6 86.2 88.585.2 5_250 90.3 92.5 89.4 87.4 84.6 88.5 3_248 90.3 90.6 90.2 93.1 92.393.4 3_250 90.3 88.7 91.1 94.3 92.3 95.1 1_250 89.8 96.2 87 85.1 84.685.2 2_249 89.8 96.2 87 89.7 100 85.2 21_248 89.7 78.8 94.3 89.7 76.995.1 10_248 88.6 88.7 88.6 86.2 88.5 85.2 5_248 87.5 90.6 86.2 89.7 92.388.5 11_249 87.5 90.6 86.2 89.7 88.5 90.2 9_250 87.5 88.7 87 89.7 84.691.8 17_250 87.5 84.9 88.6 85.1 84.6 85.2 21_249 87.4 80.8 90.2 86.280.8 88.5 7_250 86.9 90.6 85.4 90.8 96.2 88.5 15_248 86.9 81.1 89.4 90.888.5 91.8 5_249 86.4 90.6 84.6 85.1 92.3 82 12_248 86.4 90.6 84.6 88.584.6 90.2 10_249 86.4 84.9 87 92 92.3 91.8 28_250 86.4 84.9 87 87.4 84.688.5 7_249 85.8 88.7 84.6 92 92.3 91.8 18_249 85.8 88.7 84.6 87.4 92.385.2 15_249 85.8 83 87 85.1 80.8 86.9 20_249 85.8 81.1 87.8 88.5 88.588.5 24_249 85.8 81.1 87.8 88.5 96.2 85.2 11_250 85.2 90.6 82.9 86.292.3 83.6 18_248 85.2 86.8 84.6 86.2 88.5 85.2

Comparative Example 1

<Early Pancreatic Cancer or Pancreatic Cancer Precursor LesionDiscriminant Performance of Existing Tumor Markers in Blood>

The concentrations of the existing tumor markers CEA and CA19-9 in bloodwere measured in the training cohort and the validation cohort obtainedin the preceding Reference Examples. In principle, when theconcentrations of these tumor markers in blood are higher than thereference values described in Non-Patent Literature 3 above (CEA: 5ng/mL, CA19-9: 37 U/mL), subjects are usually suspected of havingcancer. Thus, whether or not the concentrations of CEA and CA19-9 inblood exceeded their reference values was examined for each sample todecide whether early pancreatic cancer or pancreatic cancer precursorlesion patients were determined as early pancreatic cancer or pancreaticcancer precursor lesion patients, and the sensitivity of each existingmarker was thereby calculated for the training cohort and validationcohort. The results are shown in Tables 5-1 and 5-2. The sensitivity ofCEA and CA19-9 was as low as 18% and 58%, respectively, in the trainingcohort, and was as low as 20% and 68%, respectively, in the validationcohort, demonstrating that neither of the markers are useful in thedetection of early pancreatic cancer or a pancreatic cancer precursorlesion (Tables 5-1 and 5-2). Furthermore, CEA and CA19-9 were totallyunable to detect IPMA low grade, one type of pancreatic cancer precursorlesion with a low malignancy, in the training cohort and the validationcohort (Tables 5-1 and 5-2).

On the other hand, as shown above in Tables 3 and 6 of Examples 1 and 2,it can be concluded that in all of the polynucleotides consisting of thenucleotide sequences represented by SEQ ID NOs: 1 to 226, combinationsof 1, 2 or more polynucleotides exhibiting sensitivity beyond theexisting early pancreatic cancer or pancreatic cancer precursor lesionmarkers are present, and thus such polynucleotides serve as excellentdiagnosis markers.

Comparative Example 2

<Performance of Existing Pancreatic Cancer miRNA Markers in Blood forEarly Pancreatic Cancer or Pancreatic Cancer Precursor Lesion>

Combinations of one or more miRNAs selected from hsa-miR-4294 (SEQ IDNO: 125), hsa-miR-6836-3p (SEQ ID NO: 231), and hsa-miR-6880-5p (SEQ IDNO: 219) included in the present invention among hsa-miR-6075,hsa-miR-4294, hsa-miR-6836-3p, hsa-miR-4530, and hsa-miR-6880-5pdescribed in Patent Literature 2 as being capable of specificallydiscriminating a pancreatic cancer patient group from other cancerpatient groups were evaluated for their early pancreatic cancer orpancreatic cancer precursor lesion discriminant performance in thetraining cohort and the validation cohort obtained in the precedingReference Examples. For example, the combination of the polynucleotidesconsisting of the nucleotide sequences represented by SEQ ID NOs: 219,125, and 231 or complementary sequences thereof showed excellentaccuracy of 93% in both of the training cohort and the validationcohort, but had sensitivity of 50% and specificity of 94.7% in thetraining cohort and sensitivity of 72.7% and specificity of 93.8% in thevalidation cohort and tended to differ in sensitivity between thetraining cohort and the validation cohort (Table 11).

TABLE 11 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 219_125_231 93 50 94.7 93 72.7 93.8

On the other hand, as shown in Tables 9-1 to 9-9 in Example 4, forexample, the measurement using the combination of three polynucleotidescomprising at least one polynucleotide selected from the groupconsisting of the polynucleotides consisting of the nucleotide sequencesrepresented by SEQ ID NOs: 119, 12, 28, 105, 137, 121, 109, 87, 5, 140,106, 2, 175, 90, 237, and 247 or complementary sequences thereof had thehighest sensitivity of 100%, the lowest sensitivity of 88.7%, thehighest specificity of 93.2%, and the lowest specificity of 88.8% in thetraining cohort and the highest sensitivity of 100%, the lowestsensitivity of 84.6%, the highest specificity of 94.2%, and the lowestspecificity of 85.3% in the validation cohort and thus showedequivalently high sensitivity and specificity between the trainingcohort and the validation cohort. From these results, it can beconcluded that the combination of two or more, preferably three or more,more preferably four or more or five or more polynucleotides comprisingat least one polynucleotide selected from the group consisting of thepolynucleotides consisting of the nucleotide sequences represented bySEQ ID NOs: 119, 12, 28, 105, 137, 121, 109, 87, 5, 140, 106, 2, 175,90, 237, and 247 or complementary sequences thereof exhibits higherdiscriminant performance than that of the combination of existingpancreatic cancer miRNA markers in blood and serves as excellentdiagnostic markers.

Comparative Example 3

<<Performance of Existing Pancreatic Cancer miRNA Markers in Blood forEarly Pancreatic Cancer or Pancreatic Cancer Precursor Lesion>

hsa-miR-145-5p (SEQ ID NO: 813), hsa-let-7f-5p (SEQ ID NO: 814),hsa-miR-146a-5p (SEQ ID NO: 815), hsa-let-7d-5p (SEQ ID NO: 816), andhsa-let-7a-5p (SEQ ID NO: 817) having 3.0 or more fold change in theirgene expression levels in a pancreatic cancer precursor lesion patientgroup relative to a healthy subject group were selected from among top30 miRNAs that had statistically significant difference in theirexpression levels between a healthy subject group and an IPMN patientgroup in Patent Literature 5 and evaluated for their early pancreaticcancer or pancreatic cancer precursor lesion discriminant performance inthe training cohort and the validation cohort obtained in the precedingReference Examples. The combination of the polynucleotides consisting ofthe nucleotide sequences represented by SEQ ID NOs: 813 to 817 orcomplementary sequences thereof had sensitivity of 63.6% and specificityof 74.5% in the training cohort and sensitivity of 54.5% and specificityof 74.7% in the validation cohort (Table 12).

TABLE 12 Training cohort Validation cohort Accuracy SensitivitySpecificity Accuracy Sensitivity Specificity SEQ ID NO: (%) (%) (%) (%)(%) (%) 813_814_815_816_817 74 63.6 74.5 73.9 54.5 74.7

On the other hand, as shown in Tables 9-1 to 9-9 in Example 4 describedabove, for example, the measurement using the combination of fivepolynucleotides comprising at least one polynucleotide selected from thegroup consisting of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 119, 12, 28, 105, 137, 121, 109,87, 5, 140, 106, 2, 175, 90, 237, and 247 or complementary sequencesthereof showed the highest sensitivity of 100%, the lowest sensitivityof 94.3%, the highest specificity of 98.6%, and the lowest specificityof 96.9% in the training cohort and the highest sensitivity of 100%, thelowest sensitivity of 92.3%, the highest specificity of 100%, and thelowest specificity of 92.3% in the validation cohort. From theseresults, it can be concluded that the combination of two or more,preferably three or more, more preferably four or more or five or morepolynucleotides comprising at least one polynucleotide selected from thegroup consisting of the polynucleotides consisting of the nucleotidesequences represented by SEQ ID NOs: 119, 12, 28, 105, 137, 121, 109,87, 5, 140, 106, 2, 175, 90, 237, and 247 or complementary sequencesthereof exhibits higher discriminant performance than that of thecombination of existing pancreatic cancer and pancreatic cancerprecursor lesion miRNA markers in blood and serves as excellentdiagnostic markers.

As shown in these Examples and Comparative Examples, the kit and themethod of the present invention can detect early pancreatic cancer or apancreatic cancer precursor lesion with higher sensitivity andspecificity than the existing tumor markers and therefore permit earlytreatment and early decision to carry out the surgical resection of acancer site. As a result, improvement in 5-year survival rate andreduction in the rate of recurrence can be achieved.

INDUSTRIAL APPLICABILITY

According to the present invention, early pancreatic cancer or apancreatic cancer precursor lesion can be detected in a subject withmuch higher sensitivity, specificity, and accuracy than conventionalmethods. This enables early detection, diagnosis and treatment of earlypancreatic cancer or a pancreatic cancer precursor lesion. According tothe present invention, early pancreatic cancer or a pancreatic cancerprecursor lesion can be detected with limited invasiveness using theblood of a subject. This allows early pancreatic cancer or a pancreaticcancer precursor lesion to be determined conveniently, rapidly, andinexpensively.

All publications, patents, and patent applications cited herein areincorporated herein by reference in their entirety.

1. A kit for the detection of early pancreatic cancer or a pancreaticcancer precursor lesion, comprising a nucleic acid(s) capable ofspecifically binding to at least one polynucleotides selected from thegroup consisting of the following early pancreatic cancer or pancreaticcancer precursor lesion markers: miR-6784-5p, miR-1181, miR-671-5p,miR-6857-5p, miR-4276, miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675,miR-6795-5p, miR-4731-5p, miR-5090, miR-3620-5p, miR-1343-5p,miR-6717-5p, miR-6825-5p, miR-6738-5p, miR-6769a-5p, miR-4728-5p,miR-652-5p, miR-4257, miR-6785-5p, miR-7110-5p, miR-6887-5p, miR-887-3p,miR-1228-5p, miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p,miR-6087, miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p,miR-128-2-5p, miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p,miR-6891-5p, miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p,miR-211-3p, miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688,miR-3917, miR-5787, miR-4632-5p, miR-6126, miR-135a-3p, miR-8063,miR-5698, miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p,miR-6829-5p, miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p,miR-6798-5p, miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920,miR-23b-3p, miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p,miR-4447, miR-6869-5p, miR-6794-5p, miR-6511a-5p, miR-6824-5p,miR-6766-3p, miR-6511a-5p, and miR-6749-5p.
 2. The kit according toclaim 1, wherein miR-6784-5p is hsa-miR-6784-5p, miR-1181 ishsa-miR-1181, miR-671-5p is hsa-miR-671-5p, miR-6857-5p ishsa-miR-6857-5p, miR-4276 is hsa-miR-4276, miR-1914-3p ishsa-miR-1914-3p, miR-149-3p is hsa-miR-149-3p, miR-937-5p ishsa-miR-937-5p, miR-4675 is hsa-miR-4675, miR-6795-5p ishsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090 ishsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p ishsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p ishsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p ishsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p ishsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p ishsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p ishsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p ishsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p ishsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p ishsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 ishsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p ishsa-miR-6732-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p ishsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 ishsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p ishsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p ishsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p ishsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p ishsa-miR-1233-5p, miR-211-3p is hsa-miR-211-3p, miR-4758-5p ishsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p,miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 ishsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p,miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 ishsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089,miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b ishsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p ishsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p ishsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6752-5p ishsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 ishsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p ishsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920,miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 ishsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p,miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p ishsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p ishsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p ishsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, and miR-6749-5p ishsa-miR-6749-5p.
 3. The kit according to claim 1, wherein the nucleicacid(s) is a polynucleotide(s) selected from the group consisting of thefollowing polynucleotides (a) to (e): (a) a polynucleotide consisting ofa nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides; (b) a polynucleotide comprising a nucleotidesequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246,248, and 250; (c) a polynucleotide consisting of a nucleotide sequencecomplementary to a nucleotide sequence represented by any of SEQ ID NOs:1 to 83, 227 to 229, 246, 248, and 250 or a nucleotide sequence derivedfrom the nucleotide sequence by the replacement of u with t, a variantthereof, a derivative thereof, or a fragment thereof comprising 15 ormore consecutive nucleotides; (d) a polynucleotide comprising anucleotide sequence complementary to a nucleotide sequence representedby any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t; and (e) a polynucleotide hybridizing understringent conditions to any of the polynucleotides (a) to (d).
 4. Thekit according to claim 1, wherein the kit further comprises a nucleicacid or nucleic acids capable of specifically binding to at least onepolynucleotides selected from the group consisting of the followingother early pancreatic cancer or pancreatic cancer precursor lesionmarkers: miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125,miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689,miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p,miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p,miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p,miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p,miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p,miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718,miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p,miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a,miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449,miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p,miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p,miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p,miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p,miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p,miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513,miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p,miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975,miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p,miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505,miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476,miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141,miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648,miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-762,miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p,miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p,miR-4463, miR-4486, miR-4730, miR-4286, and miR-4739.
 5. The kitaccording to claim 4, wherein miR-1908-5p is hsa-miR-1908-5p,miR-6729-5p is hsa-miR-6729-5p, miR-5195-3p is hsa-miR-5195-3p, miR-638is hsa-miR-638, miR-6125 is hsa-miR-6125, miR-3178 is hsa-miR-3178,miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-4723-5p ishsa-miR-4723-5p, miR-4746-3p is hsa-miR-4746-3p, miR-4689 ishsa-miR-4689, miR-6816-5p is hsa-miR-6816-5p, miR-6757-5p ishsa-miR-6757-5p, miR-71109-5p is hsa-miR-7109-5p, miR-6724-5p ishsa-miR-6724-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6875-5p ishsa-miR-6875-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4508 ishsa-miR-4508, miR-6085 is hsa-miR-6085, miR-6779-5p is hsa-miR-6779-5p,miR-642a-3p is hsa-miR-642a-3p, miR-4695-5p is hsa-miR-4695-5p,miR-7847-3p is hsa-miR-7847-3p, miR-3197 is hsa-miR-3197, miR-6769b-5pis hsa-miR-6769b-5p, miR-7641 is hsa-miR-7641, miR-187-5p ishsa-miR-187-5p, miR-3185 is hsa-miR-3185, miR-2861 is hsa-miR-2861,miR-3940-5p is hsa-miR-3940-5p, miR-1203 is hsa-miR-1203, miR-615-5p ishsa-miR-615-5p, miR-4787-5p is hsa-miR-4787-5p, miR-1343-3p ishsa-miR-1343-3p, miR-6813-5p is hsa-miR-6813-5p, miR-1225-5p ishsa-miR-1225-5p, miR-602 is hsa-miR-602, miR-4488 is hsa-miR-4488,miR-125a-3p is hsa-miR-125a-3p, miR-5100 is hsa-miR-5100, miR-4294 ishsa-miR-4294, miR-1231 is hsa-miR-1231, miR-6765-3p is hsa-miR-6765-3p,miR-4442 is hsa-miR-4442, miR-718 is hsa-miR-718, miR-6780b-5p ishsa-miR-6780b-5p, miR-6090 is hsa-miR-6090, miR-6845-5p ishsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 is hsa-miR-4467,miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271, miR-4673 ishsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 is hsa-miR-1469,miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a, miR-6791-5p ishsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p ishsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p, miR-4417 ishsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p is hsa-miR-4707-3p,miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p is hsa-miR-5585-3p,miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072, miR-296-5p ishsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 is hsa-miR-4454,miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290, miR-3622a-5pis hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p, miR-675-5p ishsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 is hsa-miR-4648,miR-1268b is hsa-miR-1268b, miR-6741-5p is hsa-miR-6741-5p, miR-6893-5pis hsa-miR-6893-5p, miR-3162-5p is hsa-miR-3162-5p, miR-642b-3p ishsa-miR-642b-3p, miR-4734 is hsa-miR-4734, miR-150-3p is hsa-miR-150-3p,miR-8089 is hsa-miR-8089, miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p ishsa-miR-7113-3p, miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p ishsa-miR-6799-5p, miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p ishsa-miR-92b-5p, miR-3679-5p is hsa-miR-3679-5p, miR-4792 ishsa-miR-4792, miR-3656 is hsa-miR-3656, miR-92a-2-5p ishsa-miR-92a-2-5p, miR-4466 is hsa-miR-4466, miR-4513 is hsa-miR-4513,miR-6781-5p is hsa-miR-6781-5p, miR-4649-5p is hsa-miR-4649-5p,miR-6775-5p is hsa-miR-6775-5p, miR-4651 is hsa-miR-4651, miR-3195 ishsa-miR-3195, miR-6726-5p is hsa-miR-6726-5p, miR-6872-3p ishsa-miR-6872-3p, miR-371a-5p is hsa-miR-371a-5p, miR-6777-5p ishsa-miR-6777-5p, miR-6789-5p is hsa-miR-6789-5p, miR-7975 ishsa-miR-7975, miR-6821-5p is hsa-miR-6821-5p, miR-4534 is hsa-miR-4534,miR-619-5p is hsa-miR-619-5p, miR-7107-5p is hsa-miR-7107-5p,miR-1228-3p is hsa-miR-1228-3p, miR-6774-5p is hsa-miR-6774-5p,miR-6805-5p is hsa-miR-6805-5p, miR-23a-3p is hsa-miR-23a-3p,miR-4665-5p is hsa-miR-41665-5p, miR-4505 is hsa-miR-4505, miR-4638-5pis hsa-miR-4638-5p, miR-24-3p is hsa-miR-24-3p, miR-3135b ishsa-miR-3135b, miR-4745-5p is hsa-miR-4745-5p, miR-128-1-5p ishsa-miR-128-1-5p, miR-4476 is hsa-miR-4476, miR-4687-3p ishsa-miR-4687-3p, miR-3665 is hsa-miR-3665, miR-6806-5p ishsa-miR-6806-5p, miR-3937 is hsa-miR-3937, miR-711 is hsa-miR-711,miR-3141 is hsa-miR-3141, miR-3188 is hsa-miR-3188, miR-4281 ishsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p, miR-6880-5p ishsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 is hsa-miR-3648,miR-6721-5p is hsa-miR-6721-5p, miR-4492 is hsa-miR-4492, miR-744-5p ishsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p ishsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p,miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 ishsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p,miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 ishsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076,miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 ishsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, andmiR-4739 is hsa-miR-4739.
 6. The kit according to claim 4, wherein thenucleic acid(s) is a polynucleotide(s) selected from the groupconsisting of the following polynucleotides (f) to (j): (f) apolynucleotide consisting of a nucleotide sequence represented by any ofSEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotide sequencederived from the nucleotide sequence by the replacement of u with t, avariant thereof, a derivative thereof, or a fragment thereof comprising15 or more consecutive nucleotides; (g) a polynucleotide comprising anucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230 to245, 247, and 249; (h) a polynucleotide consisting of a nucleotidesequence complementary to a nucleotide sequence represented by any ofSEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotide sequencederived from the nucleotide sequence by the replacement of u with t, avariant thereof, a derivative thereof, or a fragment thereof comprising15 or more consecutive nucleotides; (i) a polynucleotide comprising anucleotide sequence complementary to a nucleotide sequence representedby any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t; and (j) a polynucleotide hybridizing understringent conditions to any of the polynucleotides (f) to (i).
 7. Adevice for the detection of early pancreatic cancer or a pancreaticcancer precursor lesion, comprising a nucleic acid(s) capable ofspecifically binding to at least one polynucleotide selected from thefollowing early pancreatic cancer or pancreatic cancer precursor lesionmarkers: miR-6784-5p, miR-1181, miR-671-5p, miR-6857-5p, miR-4276,miR-1914-3p, miR-149-3p, miR-937-5p, miR-4675, miR-6795-5p, miR-4731-5p,miR-5090, miR-3620-5p, miR-1343-5p, miR-6717-5p, miR-6825-5p,miR-6738-5p, miR-6769a-5p, miR-4728-5p, miR-652-5p, miR-4257,miR-6785-5p, miR-7110-5p, miR-6887-5p, miR-887-3p, miR-1228-5p,miR-5572, miR-6782-5p, miR-4298, miR-6786-5p, miR-5010-5p, miR-6087,miR-6765-5p, miR-6732-5p, miR-6787-5p, miR-6737-5p, miR-128-2-5p,miR-4270, miR-6861-5p, miR-6756-5p, miR-1229-5p, miR-6891-5p,miR-6848-5p, miR-1237-5p, miR-30c-1-3p, miR-1233-5p, miR-211-3p,miR-4758-5p, miR-614, miR-6746-5p, miR-1915-5p, miR-4688, miR-3917,miR-5787, miR-4632-5p, miR-6126, miR-135a-3p, miR-8063, miR-5698,miR-6089, miR-498, miR-296-3p, miR-4419b, miR-6802-5p, miR-6829-5p,miR-6803-5p, miR-1199-5p, miR-6840-3p, miR-6752-5p, miR-6798-5p,miR-6131, miR-4667-5p, miR-6510-5p, miR-4690-5p, miR-920, miR-23b-3p,miR-4448, miR-2110, miR-4706, miR-7845-5p, miR-6808-5p, miR-4447,miR-6869-5p, miR-6794-5p, miR-6511a-5p, miR-6824-5p, miR-6766-3p,miR-6511a-5p, and miR-6749-5p.
 8. The device according to claim 7,wherein miR-6784-5p is hsa-miR-6784-5p, miR-1181 is hsa-miR-1181,miR-671-5p is hsa-miR-671-5p, miR-6857-5p is hsa-miR-6857-5p, miR-4276is hsa-miR-4276, miR-1914-3p is hsa-miR-1914-3p, miR-149-3p ishsa-miR-149-3p, miR-937-5p is hsa-miR-937-5p, miR-4675 is hsa-miR-4675,miR-6795-5p is hsa-miR-6795-5p, miR-4731-5p is hsa-miR-4731-5p, miR-5090is hsa-miR-5090, miR-3620-5p is hsa-miR-3620-5p, miR-1343-5p ishsa-miR-1343-5p, miR-6717-5p is hsa-miR-6717-5p, miR-6825-5p ishsa-miR-6825-5p, miR-6738-5p is hsa-miR-6738-5p, miR-6769a-5p ishsa-miR-6769a-5p, miR-4728-5p is hsa-miR-4728-5p, miR-652-5p ishsa-miR-652-5p, miR-4257 is hsa-miR-4257, miR-6785-5p ishsa-miR-6785-5p, miR-7110-5p is hsa-miR-7110-5p, miR-6887-5p ishsa-miR-6887-5p, miR-887-3p is hsa-miR-887-3p, miR-1228-5p ishsa-miR-1228-5p, miR-5572 is hsa-miR-5572, miR-6782-5p ishsa-miR-6782-5p, miR-4298 is hsa-miR-4298, miR-6786-5p ishsa-miR-6786-5p, miR-5010-5p is hsa-miR-5010-5p, miR-6087 ishsa-miR-6087, miR-6765-5p is hsa-miR-6765-5p, miR-6732-5p ishsa-miR-6732-5p, miR-6787-5p is hsa-miR-6787-5p, miR-6737-5p ishsa-miR-6737-5p, miR-128-2-5p is hsa-miR-128-2-5p, miR-4270 ishsa-miR-4270, miR-6861-5p is hsa-miR-6861-5p, miR-6756-5p ishsa-miR-6756-5p, miR-1229-5p is hsa-miR-1229-5p, miR-6891-5p ishsa-miR-6891-5p, miR-6848-5p is hsa-miR-6848-5p, miR-1237-5p ishsa-miR-1237-5p, miR-30c-1-3p is hsa-miR-30c-1-3p, miR-1233-5p ishsa-miR-1233-5p, miR-2111-3p is hsa-miR-211-3p, miR-4758-5p ishsa-miR-4758-5p, miR-614 is hsa-miR-614, miR-6746-5p is hsa-miR-6746-5p,miR-1915-5p is hsa-miR-1915-5p, miR-4688 is hsa-miR-4688, miR-3917 ishsa-miR-3917, miR-5787 is hsa-miR-5787, miR-4632-5p is hsa-miR-4632-5p,miR-6126 is hsa-miR-6126, miR-135a-3p is hsa-miR-135a-3p, miR-8063 ishsa-miR-8063, miR-5698 is hsa-miR-5698, miR-6089 is hsa-miR-6089,miR-498 is hsa-miR-498, miR-296-3p is hsa-miR-296-3p, miR-4419b ishsa-miR-4419b, miR-6802-5p is hsa-miR-6802-5p, miR-6829-5p ishsa-miR-6829-5p, miR-6803-5p is hsa-miR-6803-5p, miR-1199-5p ishsa-miR-1199-5p, miR-6840-3p is hsa-miR-6840-3p, miR-6752-5p ishsa-miR-6752-5p, miR-6798-5p is hsa-miR-6798-5p, miR-6131 ishsa-miR-6131, miR-4667-5p is hsa-miR-4667-5p, miR-6510-5p ishsa-miR-6510-5p, miR-4690-5p is hsa-miR-4690-5p, miR-920 is hsa-miR-920,miR-23b-3p is hsa-miR-23b-3p, miR-4448 is hsa-miR-4448, miR-2110 ishsa-miR-2110, miR-4706 is hsa-miR-4706, miR-7845-5p is hsa-miR-7845-5p,miR-6808-5p is hsa-miR-6808-5p, miR-4447 is hsa-miR-4447, miR-6869-5p ishsa-miR-6869-5p, miR-6794-5p is hsa-miR-6794-5p, miR-6511a-5p ishsa-miR-6511a-5p, miR-6824-5p is hsa-miR-6824-5p, miR-6766-3p ishsa-miR-6766-3p, miR-6511a-5p is hsa-miR-6511a-5p, and miR-6749-5p ishsa-miR-6749-5p.
 9. The device according to claim 7, wherein the nucleicacid(s) is a polynucleotide(s) selected from the group consisting of thefollowing polynucleotides (a) to (e): (a) a polynucleotide consisting ofa nucleotide sequence represented by any of SEQ ID NOs: 1 to 83, 227 to229, 246, 248, and 250 or a nucleotide sequence derived from thenucleotide sequence by the replacement of u with t, a variant thereof, aderivative thereof, or a fragment thereof comprising 15 or moreconsecutive nucleotides; (b) a polynucleotide comprising a nucleotidesequence represented by any of SEQ ID NOs: 1 to 83, 227 to 229, 246,248, and 250; (c) a polynucleotide consisting of a nucleotide sequencecomplementary to a nucleotide sequence represented by any of SEQ ID NOs:1 to 83, 227 to 229, 246, 248, and 250 or a nucleotide sequence derivedfrom the nucleotide sequence by the replacement of u with t, a variantthereof, a derivative thereof, or a fragment thereof comprising 15 ormore consecutive nucleotides; (d) a polynucleotide comprising anucleotide sequence complementary to a nucleotide sequence representedby any of SEQ ID NOs: 1 to 83, 227 to 229, 246, 248, and 250 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t; and (e) a polynucleotide hybridizing understringent conditions to any of the polynucleotides (a) to (d).
 10. Thedevice according to claim 7, wherein the device further comprises anucleic acid(s) capable of specifically binding to at least onepolynucleotides selected from the group consisting of the followingother early pancreatic cancer or pancreatic cancer precursor lesionmarkers: miR-1908-5p, miR-6729-5p, miR-5195-3p, miR-638, miR-6125,miR-3178, miR-3196, miR-8069, miR-4723-5p, miR-4746-3p, miR-4689,miR-6816-5p, miR-6757-5p, miR-7109-5p, miR-6724-5p, miR-1225-3p,miR-6875-5p, miR-7108-5p, miR-4508, miR-6085, miR-6779-5p, miR-642a-3p,miR-4695-5p, miR-7847-3p, miR-3197, miR-6769b-5p, miR-7641, miR-187-5p,miR-3185, miR-2861, miR-3940-5p, miR-1203, miR-615-5p, miR-4787-5p,miR-1343-3p, miR-6813-5p, miR-1225-5p, miR-602, miR-4488, miR-125a-3p,miR-5100, miR-4294, miR-1231, miR-6765-3p, miR-4442, miR-718,miR-6780b-5p, miR-6090, miR-6845-5p, miR-4741, miR-4467, miR-4707-5p,miR-4271, miR-4673, miR-3184-5p, miR-1469, miR-4640-5p, miR-663a,miR-6791-5p, miR-6826-5p, miR-4433b-3p, miR-1915-3p, miR-4417, miR-4449,miR-4707-3p, miR-3180-3p, miR-5585-3p, miR-1268a, miR-8072, miR-296-5p,miR-204-3p, miR-4454, miR-6722-3p, miR-1290, miR-3622a-5p, miR-939-5p,miR-675-5p, miR-3131, miR-4648, miR-1268b, miR-6741-5p, miR-6893-5p,miR-3162-5p, miR-642b-3p, miR-4734, miR-150-3p, miR-8089, miR-6805-3p,miR-7113-3p, miR-6850-5p, miR-6799-5p, miR-6768-5p, miR-92b-5p,miR-3679-5p, miR-4792, miR-3656, miR-92a-2-5p, miR-4466, miR-4513,miR-6781-5p, miR-4649-5p, miR-6775-5p, miR-4651, miR-3195, miR-6726-5p,miR-6872-3p, miR-371a-5p, miR-6777-5p, miR-6789-5p, miR-7975,miR-6821-5p, miR-4534, miR-619-5p, miR-7107-5p, miR-1228-3p,miR-6774-5p, miR-6805-5p, miR-23a-3p, miR-4665-5p, miR-4505,miR-4638-5p, miR-24-3p, miR-3135b, miR-4745-5p, miR-128-1-5p, miR-4476,miR-4687-3p, miR-3665, miR-6806-5p, miR-3937, miR-711, miR-3141,miR-3188, miR-4281, miR-5196-5p, miR-6880-5p, miR-3960, miR-3648,miR-6721-5p, miR-4492, miR-744-5p, miR-7704, miR-4749-5p, miR-762,miR-6836-3p, miR-6727-5p, miR-4739, miR-7977, miR-4484, miR-6515-3p,miR-373-5p, miR-4258, miR-4674, miR-3180, miR-6076, miR-1238-5p,miR-4463, miR-4486, miR-4730, miR-4286, and miR-4739.
 11. The deviceaccording to claim 10, wherein miR-1908-5p is hsa-miR-1908-5p,miR-6729-5p is hsa-miR-6729-5p, miR-5195-3p is hsa-miR-5195-3p, miR-638is hsa-miR-638, miR-6125 is hsa-miR-6125, miR-3178 is hsa-miR-3178,miR-3196 is hsa-miR-3196, miR-8069 is hsa-miR-8069, miR-4723-5p ishsa-miR-4723-5p, miR-4746-3p is hsa-miR-4746-3p, miR-4689 ishsa-miR-4689, miR-6816-5p is hsa-miR-6816-5p, miR-6757-5p ishsa-miR-6757-5p, miR-7109-5p is hsa-miR-7109-5p, miR-6724-5p ishsa-miR-6724-5p, miR-1225-3p is hsa-miR-1225-3p, miR-6875-5p ishsa-miR-6875-5p, miR-7108-5p is hsa-miR-7108-5p, miR-4508 ishsa-miR-4508, miR-6085 is hsa-miR-6085, miR-6779-5p is hsa-miR-6779-5p,miR-642a-3p is hsa-miR-642a-3p, miR-4695-5p is hsa-miR-4695-5p,miR-7847-3p is hsa-miR-7847-3p, miR-3197 is hsa-miR-3197, miR-6769b-5pis hsa-miR-6769b-5p, miR-7641 is hsa-miR-7641, miR-187-5p ishsa-miR-187-5p, miR-3185 is hsa-miR-3185, miR-2861 is hsa-miR-2861,miR-3940-5p is hsa-miR-3940-5p, miR-1203 is hsa-miR-1203, miR-615-5p ishsa-miR-615-5p, miR-4787-5p is hsa-miR-4787-5p, miR-1343-3p ishsa-miR-1343-3p, miR-6813-5p is hsa-miR-6813-5p, miR-1225-5p ishsa-miR-1225-5p, miR-602 is hsa-miR-602, miR-4488 is hsa-miR-4488,miR-125a-3p is hsa-miR-125a-3p, miR-5100 is hsa-miR-5100, miR-4294 ishsa-miR-4294, miR-1231 is hsa-miR-1231, miR-6765-3p is hsa-miR-6765-3p,miR-4442 is hsa-miR-4442, miR-718 is hsa-miR-718, miR-6780b-5p ishsa-miR-6780b-5p, miR-6090 is hsa-miR-6090, miR-6845-5p ishsa-miR-6845-5p, miR-4741 is hsa-miR-4741, miR-4467 is hsa-miR-4467,miR-4707-5p is hsa-miR-4707-5p, miR-4271 is hsa-miR-4271, miR-4673 ishsa-miR-4673, miR-3184-5p is hsa-miR-3184-5p, miR-1469 is hsa-miR-1469,miR-4640-5p is hsa-miR-4640-5p, miR-663a is hsa-miR-663a, miR-6791-5p ishsa-miR-6791-5p, miR-6826-5p is hsa-miR-6826-5p, miR-4433b-3p ishsa-miR-4433b-3p, miR-1915-3p is hsa-miR-1915-3p, miR-4417 ishsa-miR-4417, miR-4449 is hsa-miR-4449, miR-4707-3p is hsa-miR-4707-3p,miR-3180-3p is hsa-miR-3180-3p, miR-5585-3p is hsa-miR-5585-3p,miR-1268a is hsa-miR-1268a, miR-8072 is hsa-miR-8072, miR-296-5p ishsa-miR-296-5p, miR-204-3p is hsa-miR-204-3p, miR-4454 is hsa-miR-4454,miR-6722-3p is hsa-miR-6722-3p, miR-1290 is hsa-miR-1290, miR-3622a-5pis hsa-miR-3622a-5p, miR-939-5p is hsa-miR-939-5p, miR-675-5p ishsa-miR-675-5p, miR-3131 is hsa-miR-3131, miR-4648 is hsa-miR-4648,miR-1268b is hsa-miR-1268b, miR-6741-5p is hsa-miR-6741-5p, miR-6893-5pis hsa-miR-6893-5p, miR-3162-5p is hsa-miR-3162-5p, miR-642b-3p ishsa-miR-642b-3p, miR-4734 is hsa-miR-4734, miR-150-3p is hsa-miR-150-3p,miR-8089 is hsa-miR-8089, miR-6805-3p is hsa-miR-6805-3p, miR-7113-3p ishsa-miR-7113-3p, miR-6850-5p is hsa-miR-6850-5p, miR-6799-5p ishsa-miR-6799-5p, miR-6768-5p is hsa-miR-6768-5p, miR-92b-5p ishsa-miR-92b-5p, miR-3679-5p is hsa-miR-3679-5p, miR-4792 ishsa-miR-4792, miR-3656 is hsa-miR-3656, miR-92a-2-5p ishsa-miR-92a-2-5p, miR-4466 is hsa-miR-4466, miR-4513 is hsa-miR-4513,miR-6781-5p is hsa-miR-6781-5p, miR-4649-5p is hsa-miR-4649-5p,miR-6775-5p is hsa-miR-6775-5p, miR-4651 is hsa-miR-4651, miR-3195 ishsa-miR-3195, miR-6726-5p is hsa-miR-6726-5p, miR-6872-3p ishsa-miR-6872-3p, miR-371a-5p is hsa-miR-371a-5p, miR-6777-5p ishsa-miR-6777-5p, miR-6789-5p is hsa-miR-6789-5p, miR-7975 ishsa-miR-7975, miR-6821-5p is hsa-miR-6821-5p, miR-4534 is hsa-miR-4534,miR-619-5p is hsa-miR-619-5p, miR-7107-5p is hsa-miR-7107-5p,miR-1228-3p is hsa-miR-1228-3p, miR-6774-5p is hsa-miR-6774-5p,miR-6805-5p is hsa-miR-6805-5p, miR-23a-3p is hsa-miR-23a-3p,miR-4665-5p is hsa-miR-4665-5p, miR-4505 is hsa-miR-4505, miR-4638-5p ishsa-miR-4638-5p, miR-24-3p is hsa-miR-24-3p, miR-3135b is hsa-miR-3135b,miR-4745-5p is hsa-miR-4745-5p, miR-128-1-5p is hsa-miR-128-1-5p,miR-4476 is hsa-miR-4476, miR-4687-3p is hsa-miR-4687-3p, miR-3665 ishsa-miR-3665, miR-6806-5p is hsa-miR-6806-5p, miR-3937 is hsa-miR-3937,miR-711 is hsa-miR-711, miR-3141 is hsa-miR-3141, miR-3188 ishsa-miR-3188, miR-4281 is hsa-miR-4281, miR-5196-5p is hsa-miR-5196-5p,miR-6880-5p is hsa-miR-6880-5p, miR-3960 is hsa-miR-3960, miR-3648 ishsa-miR-3648, miR-6721-5p is hsa-miR-6721-5p, miR-4492 is hsa-miR-4492,miR-744-5p is hsa-miR-744-5p, miR-7704 is hsa-miR-7704, miR-4749-5p ishsa-miR-4749-5p, miR-762 is hsa-miR-762, miR-6836-3p is hsa-miR-6836-3p,miR-6727-5p is hsa-miR-6727-5p, miR-4739 is hsa-miR-4739, miR-7977 ishsa-miR-7977, miR-4484 is hsa-miR-4484, miR-6515-3p is hsa-miR-6515-3p,miR-373-5p is hsa-miR-373-5p, miR-4258 is hsa-miR-4258, miR-4674 ishsa-miR-4674, miR-3180 is hsa-miR-3180, miR-6076 is hsa-miR-6076,miR-1238-5p is hsa-miR-1238-5p, miR-4463 is hsa-miR-4463, miR-4486 ishsa-miR-4486, miR-4730 is hsa-miR-4730, miR-4286 is hsa-miR-4286, andmiR-4739 is hsa-miR-4739.
 12. The device according to claim 10, whereinthe nucleic acid(s) is/are a polynucleotide(s) selected from the groupconsisting of the following polynucleotides (f) to (j): (f) apolynucleotide consisting of a nucleotide sequence represented by any ofSEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotide sequencederived from the nucleotide sequence by the replacement of u with t, avariant thereof, a derivative thereof, or a fragment thereof comprising15 or more consecutive nucleotides; (g) a polynucleotide comprising anucleotide sequence represented by any of SEQ ID NOs: 84 to 226, 230 to245, 247, and 249; (h) a polynucleotide consisting of a nucleotidesequence complementary to a nucleotide sequence represented by any ofSEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or a nucleotide sequencederived from the nucleotide sequence by the replacement of u with t, avariant thereof, a derivative thereof, or a fragment thereof comprising15 or more consecutive nucleotides; (i) a polynucleotide comprising anucleotide sequence complementary to a nucleotide sequence representedby any of SEQ ID NOs: 84 to 226, 230 to 245, 247, and 249 or anucleotide sequence derived from the nucleotide sequence by thereplacement of u with t; and (j) a polynucleotide hybridizing understringent conditions to any of the polynucleotides (f) to (i).
 13. Thedevice according to claim 7, wherein the device is a device formeasurement by a hybridization technique.
 14. The device according toclaim 13, wherein the hybridization technique is a nucleic acid arraytechnique.
 15. A method for detecting early pancreatic cancer or apancreatic cancer precursor lesion in a subject, comprising: measuringan expression level(s) of a target nucleic acid(s) in a sample from thesubject using a kit according to claim 1; and evaluating in vitrowhether or not the subject has early pancreatic cancer or a pancreaticcancer precursor lesion using both of the measured expression level(s)and a control expression level(s) in a sample from a healthy subjectmeasured in the same way, to detect the presence or absence of earlypancreatic cancer or a pancreatic cancer precursor lesion in thesubject.
 16. A method for detecting early pancreatic cancer or apancreatic cancer precursor lesion in a subject, comprising: measuringan expression level(s) of a target gene(s) in a sample from the subjectusing a kit according to claim 1; and assigning the expression level(s)of the target gene(s) in the sample from the subject to a discriminantto evaluate the presence or absence of early pancreatic cancer or apancreatic cancer precursor lesion, wherein the discriminant is preparedwith the gene expression level(s) in a sample(s) from a subject(s) knownto have early pancreatic cancer or a pancreatic cancer precursor lesionand the gene expression level(s) in a sample(s) from a healthysubject(s) as supervising samples and is capable of discriminating anearly pancreatic cancer or pancreatic cancer precursor lesion patientfrom a healthy subject.
 17. The method according to claim 15, whereinthe subject is a human.
 18. The method according to any claim 15,wherein the sample is blood, serum, or plasma.